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Acute myocardial infarction can be caused by ischemia/reperfusion (I/R) injury; however, the mechanism underlying I/R is not completely understood. The present study investigated the functions and mechanisms underlying microRNA (miR)‑494 in I/R‑induced cardiomyocyte apoptosis and autophagy. Hypoxia/reoxygenation (H/R)‑treated H9c2 rat myocardial cells were used as an in vitro I/R injury model. Apoptosis and autophagy were analyzed by Cell Counting Kit‑8 assay, Lactic dehydrogenase and superoxide dismutase assay, flow cytometry, TUNEL staining and western blotting. Reverse transcription‑quantitative PCR demonstrated that, H9c2 cells treated with 12 h hypoxia and 3 h reoxygenation displayed significantly downregulated miR‑494 expression levels compared with control cells. Compared with the corresponding negative control (NC) groups, miR‑494 mimic reduced H/R‑induced cell apoptosis and autophagy, whereas miR‑494 inhibitor displayed the opposite effects. Silent information regulator 1 (SIRT1) was identified as a target gene of miR‑494. Furthermore, miR‑494 inhibitor‑mediated effects on H/R‑induced cardiomyocyte apoptosis and autophagy were partially reversed by SIRT1 knockdown. Moreover, compared with si‑NC, SIRT1 knockdown significantly increased the phosphorylation levels of PI3K, AKT and mTOR in H/R‑treated and miR‑494 inhibitor‑transfected H9c2 cells. Collectively, the results indicated that miR‑494 served a protective role against H/R‑induced cardiomyocyte apoptosis and autophagy by directly targeting SIRT1, suggesting that miR‑494 may serve as a novel therapeutic target for myocardial I/R injury.

Sepsis is a serious clinical condition characterized by systemic inflammation. The long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) was validated to partake in the development of sepsis. The present study aimed to investigate the potential mechanism of HULC in lipopolysaccharide (LPS)-induced sepsis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis was employed to examine the expression of HULC, microRNA (miR)-128-3p, Rac family small GTPase 1 (RAC1) and pro-inflammatory factors [IL-6, TNF-α, intercellular adhesion molecule (ICAM1) and vascular cell adhesion molecule (VCAM1)] in the serum of patients with sepsis or LPS-induced human dermal microvascular endothelial cells (HMEC-1). Flow cytometry and western blot assays were performed to detect cell apoptosis. The targeted relationship among HULC, miR-128-3p and RAC1 was confirmed by a dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP) assay and RNA pull-down assay. HULC and RAC1 were found to be upregulated, and miR-128-3p was downregulated in the serum of patients with sepsis and LPS-stimulated HMEC-1 cells. LPS promoted apoptosis and inflammation, which were decreased by silencing of HULC. HULC targeted miR-128-3p and negatively regulated its expression. HULC knockdown protected HMEC-1 cells from LPS-induced injury by upregulating miR-128-3p. RAC1 was a target of miR-128-3p, and gain of RAC1 also relieved the silencing of HULC-mediated suppressive effects on apoptosis and inflammation in LPS-stimulated HMEC-1 cells. In conclusion, HULC knockdown partially reversed LPS-induced sepsis via the regulation of miR-128-3p/RAC1 axis.

FGD5 antisense RNA 1 (FGD5‑AS1) is a long non‑coding RNA in acute myocardial infarction (AMI), which is primarily caused by myocardial ischemia‑hypoxia. Retinoid acid receptor‑related orphan receptor α (RORA) is a key protector in maintaining heart function. However, the roles of FGD5‑AS1 and RORA in AMI have not previously been elucidated. The present study investigated the effect and mechanism of FGD5‑AS1 and RORA in human cardiomyocyte AC16 cells under hypoxia. Reverse transcription‑quantitative PCR and western blotting demonstrated that FGD5‑AS1 and RORA were downregulated in the serum of patients with AMI and hypoxia‑challenged AC16 cells. Functional experiments were performed via assays, flow cytometry and western blotting. In response to hypoxia, superoxide dismutase (SOD) activity was inhibited, but apoptosis rate and levels of reactive oxygen species and malondialdehyde were promoted in AC16 cells, accompanied by increased Bax and cleaved caspase‑3 expression levels, and decreased SOD2 and glutathione peroxidase 1 expression levels. However, hypoxia‑induced oxidative stress and apoptosis in AC16 cells were attenuated by ectopic expression of FGD5‑AS1 or RORA. Moreover, silencing RORA counteracted the suppressive role of FGD5‑AS1 overexpression in hypoxic injury. FGD5‑AS1 controlled RORA expression levels via microRNA‑195‑5p (miR‑195), as confirmed by dual‑luciferase reporter and RNA pull‑down assays. Consistently, miR‑195 knockdown suppressed hypoxia‑induced oxidative stress and apoptosis in AC16 cells, which was abrogated by downregulating FGD5‑AS1 or RORA. In conclusion, FGD5‑AS1 modulated hypoxic injury in human cardiomyocytes partially via the miR‑195/RORA axis, suggesting FGD5‑AS1 as a potential target in interfering with the progression of AMI.

Long non‑coding RNAs (lncRNAs) affect atherosclerosis by regulating the physiological and pathological processes of endothelial cells; however, the role of lncRNA WEE2 antisense RNA 1 (WEE2‑AS1) in arteriosclerosis obliterans (ASO) is not completely understood. The present study aimed to explore the function of lncRNA WEE2‑AS1 in human vascular endothelial cells. The results indicated that lncRNA WEE2‑AS1 was significantly elevated in plasma and artery tissue samples of patients with ASO compared with healthy controls. The fluorescence in situ hybridization results suggested that lncRNA WEE2‑AS1 was expressed in the cytoplasm and nuclei of primary human umbilical vein endothelial cells (HUVECs). The Cell Counting Kit‑8 assay results suggested that lncRNA WEE2‑AS1 knockdown significantly promoted HUVEC viability, whereas lncRNA WEE2‑AS1 overexpression inhibited HUVEC viability compared with the negative control groups. Furthermore, analysis of the cell cycle by flow cytometry indicated that lncRNA WEE2‑AS1 knockdown significantly decreased the proportion of cells in the G0/G1 phase and significantly increased the proportion of cells in the G2/M phase compared with the negative control group. However, lncRNA WEE2‑AS1 overexpression had no significant effect on cell cycle distribution compared with the negative control group. The western blotting results indicated that lncRNA WEE2‑AS1 knockdown significantly reduced the expression levels of phosphorylated cyclin dependent kinase 1, WEE1 homolog 2 and myelin transcription factor 1, but increased the expression level of cell division cycle 25B compared with the negative control group. lncRNA WEE2‑AS1 overexpression displayed the opposite effect on protein expression. Collectively, the present study suggested that lncRNA WEE2‑AS1 was significantly upregulated in ASO and may serve a role in regulating human vascular endothelial cell viability. Further investigation into lncRNA WEE2‑AS1 may broaden the current understanding of the molecular mechanism underlying ASO, and aid with the identification of specific probes and precise targeted drugs for the diagnosis and treatment of ASO.

Epithelial-mesenchymal transition (EMT) serves an important regulatory role in obstructive nephropathy and renal fibrosis. As an intracellular energy sensor, AMP-activated protein kinase (AMPK) is essential in the process of EMT. The aim of the present study was to elucidate changes in the expression levels of AMPKα2 and which AMPKα2 genes play a role during EMT. TGF-β1 was used to induce EMT in normal rat renal tubular epithelial (NRK-52E) cells. The short hairpin AMPKα2 lentivirus was used to interfere with AMPKα2 expression levels in EMT-derived NRK-52E cells and AMPKα2 expression levels and EMT were detected. Differential gene expression levels following AMPKα2 knockdown in EMT-derived NRK-52E cells were assessed via gene microarray. Potential regulatory pathways were analyzed using ingenuity pathway analysis (IPA) and differentially expressed genes were partially verified by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. AMPKα2 was upregulated in TGF-β1-induced EMT-derived NRK-52E cells. EMT progression was significantly inhibited following downregulation of expression levels of AMPKα2 by shAMPKα2 lentivirus. A total of 1,588 differentially expressed genes were detected following AMPKα2 knockdown in NRK-52E cells in which EMT occurred. The ERK/MAPK pathway was significantly impaired following AMPKα2 knockdown, as indicated by IPA analysis. Furthermore, RT-qPCR and western blot results demonstrated that the expression levels of AMPKα2, v-ets erythroblastosis virus E26 oncogene homolog-1 (ETS1) and ribosomal protein S6 kinase A1 (RPS6KA1) were upregulated following EMT in NRK-52E cells, whereas the expression levels of ETS1 and RPS6KA1 were downregulated following AMPKα2 knockdown. It was concluded that AMPKα2 plays a key role in the regulation of rat renal tubular EMT, which may be achieved by modulating ETS1 and RPS6KA1 in the ERK/MAPK pathway.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders characterized by hyperandrogenism, polycystic ovaries and ovulatory dysfunction. Several studies have suggested that the aberrant expression of microRNAs (miRNAs/miRs) plays an important role in the pathogenesis of PCOS; however, the role and underlying mechanisms of miR-132 in the development of PCOS remain unclear. In the present study, the expression of miR-132 in granulosa cells (GCs) derived from 26 patients with PCOS and 30 healthy controls was detected by reverse transcription-quantitative PCR (RT-qPCR). The apoptosis of GCs was examined using a TUNEL assay. The human ovarian granulosa-like tumor cell line, KGN, was cultured for Cell Counting Kit-8 assays following the overexpression or knockdown of miR-132. TargetScan was applied to identify the potential targets of miR-132, which was further verified by a luciferase assay, RT-qPCR and western blotting. The expression of miR-132 was decreased in GCs from patients with PCOS. Moreover, the GCs of patients with PCOS exhibited significantly increased apoptotic nuclei. Furthermore, the overexpression of miR-132 inhibited the viability of KGN cells. In addition, the results verified that miR-132 directly targeted forkhead box protein A1 (Foxa1), the knockdown of which suppressed KGN cell viability. On the whole, the findings of the present study demonstrated that miR-132 inhibited cell viability and induced apoptosis by directly interacting with Foxa1. Thus, miR-132 may be a potential target for the treatment of patients with PCOS.

Cervical cancer (CC) is a frequently occurring cancer in women with a high mortality rate. Despite improvements to therapeutic strategies, the survival outcome for patients with CC remains poor. Therefore, the present study aimed to investigate the molecular mechanism underlying CC inhibition involving microRNA (miR)‑140‑5p and flap structure‑specific endonuclease 1 (FEN1). Bioinformatics analysis was conducted, which identified that FEN1 was associated with CC cell cycle progression. Subsequently, 3'untranslated region reporter assays were performed to assess the regulatory relationship between FEN1 mRNA and miR‑140‑5p. Functional assays, including EdU staining assay, flow cytometry, and wound healing assays, were conducted to observe CC cell phenotypes induced by alterations to miR‑140‑5p and FEN1 expression levels. FEN1 expression was high and miR‑140‑5p expression was low in CC tissues and cell lines compared with adjacent healthy tissues and a normal cervical epithelial cell line, respectively. miR‑140‑5p knockdown reversed small interfering RNA‑FEN1‑mediated suppressive effects on CC cell phenotypes, potentially via inducing cell cycle arrest at the G1 phase. Therefore, the present study suggested that miR‑140‑5p may serve as an antitumorigenesis factor in CC by targeting FEN1 mRNA.

Circular RNAs (circRNAs) have crucial roles in various diseases; however, the mechanisms of action underlying circRNAs in the occurrence and development of diabetic nephropathy (DN) remains largely unknown. The present study investigated the differentially expressed circRNAs in the DN mice kidney cortex using circRNA sequencing and elucidated the role of circRNAs in mesangial cells. It was revealed that 40 circRNAs were unconventionally expressed, including 18 upregulated circRNAs and 22 downregulated circRNAs. Furthermore, circ_0000491 levels were significantly augmented in both DN mice and high glucose (HG, 30 mM)-induced mouse mesangial cells (MES13 cells). Knockdown of circ_0000491 significantly suppressed the increase of vimentin, fibronectin and α-smooth muscle actin, as well as collagen type I, III and IV, whilst reversing the decrease of E-cadherin in HG-induced MES13 cells. It was further revealed that circRNA_0000491 sponged miR-101b and that miR-101b directly targets TGFβRI. In addition, the expression levels of miR-101b were negatively associated with the transcriptional level of circRNA_0000491 and miR-101b inhibitors reversed the suppression of extracellular matrix (ECM)-associated protein synthesis mediated by knocking-down circRNA_0000491. In conclusion, the present study investigated the circRNA_0000491/miR-101b/TGFβRI axis in ECM accumulation and fibrosis-associated protein expression levels of mesangial cells, which suggested that circRNA_0000491 may be beneficial for the development of an effective therapeutic target for DN.

Previous studies have reported that long non‑coding RNAs (lncRNAs) have a significant role in the metastasis of tumors, including ovarian cancer (OC). The aim of the present study was to demonstrate the function and working mechanism of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in OC. The expressions of NEAT1 in OC were measured by reverse transcription‑quantitativePCR (RT‑qPCR). The effects of NEAT1 on cell proliferation, invasion, migration and epithelial‑mesenchymal transition (EMT) were detected by Cell Counting Kit‑8, transwell and wound healing assays, and western blotting. Dual‑luciferase reporter assays were performed to confirm the correlated between NEAT and miR‑1321, miR‑1321 and TJP3. The effect of NEAT1 on miR‑1321 and TJP3 was confirmed by RT‑qPCR and western blotting. Elevated expression of NEAT1 was observed in OC cell lines, and NEAT1 expression was found to be positively related to the expression of tight junction protein 3 (TJP3), which is important in cancer development. Moreover, the present results indicated that NEAT1 and TJP3 expression levels were negatively correlated with microRNA (miR)‑1321 expression in OC. Knockdown of NEAT1 attenuated the migration and invasion of OC cells, as well as increased miR‑1321 expression and in turn led to the reduction of TJP3. Thus, the present study demonstrated that NEAT1 regulates TJP3 expression by sponging miR‑1321 and enhances the epithelial‑mesenchymal transition, invasion and migration of OC cells. Overall, the present study identified the function and mechanism of NEAT1 in OC, suggesting that NEAT1 may be a promising therapeutic target for OC metastasis.

Lung adenocarcinoma (LUAD), a major subtype of lung cancer, is the leading cause of cancer‑related mortality worldwide. Previous studies have determined the role of the protein arginine methyltransferases (PRMTs) in the physiology and pathology of LUAD. However, to the best of our knowledge, no empirical studies have been performed determining the association between protein arginine methyltransferase 6 (PRMT6) and LUAD. The present study aimed to determine the expression levels of PRMT6 in LUAD and its association with the clinicopathological characteristics. The effect of PRMT6 knockdown on cell growth was analyzed and chromatin immunoprecipitation (ChIP) assay was used to investigate the regulatory mechanisms of PRMT6 on downstream gene expression. In addition, a xenograft model was used to determine whether the PRMT6‑regulated expression levels of p18 in vitro could be validated in vivo. PRMT6 overexpression in LUAD is associated with high clinical stage, lymph node metastasis and poor clinical outcomes. Furthermore, the silencing of PRMT6 significantly reduced the enrichment of Histone H3 asymmetric demethylation at arginine 2 in the promoter region of the p18 gene, thereby activating the expression of the gene. This, in turn, induced G1/S phase cell cycle arrest, resulting in the inhibition of cell proliferation. The xenograft model also suggested that PRMT6 suppressed LUAD development by activating p18 expression in vivo. In conclusion, the findings of the present study suggested that PRMT6 may serve as an oncogene in the progression of LUAD through epigenetically suppressing p18 expression. Thus, PRMT6 may represent a novel potential therapeutic target for LUAD.

Acute gouty arthritis (AGA) is characterized by the accumulation of pro‑inflammatory cytokines, which are immunological responses to monosodium urate (MSU) crystals. It has been demonstrated that long non‑coding RNA (lncRNA)‑MM2P is a novel regulator of M2 polarization of macrophages. The aim of the present study was to investigate whether lncRNA‑MM2P regulates the MSU‑induced inflammatory process. In cell models of RAW 264.7 and THP‑1‑derived macrophages, decreased expression of lncRNA‑MM2P was observed in lipopolysaccharide‑ and MSU‑treated macrophages, which was accompanied with obvious inflammatory responses. Using small interfering RNA to knockdown lncRNA‑MM2P led to the upregulation of MSU‑mediated inflammatory responses, both in RAW 264.7 and THP‑1‑derived macrophages. In conclusion, lncRNA‑MM2P could be an important regulator of MSU‑induced inflammation, and therefore could be involved in the development of AGA.

As a member of the integrin family, integrin α3β1 (ITGA3) has been linked to intercellular communication and serves an important role in the signaling among cells and the extracellular matrix. MicroRNA (miR)‑199a‑5p has been demonstrated to be related to the pathogenesis and progression of multiple malignant diseases. However, the biological functions of miR‑199a‑5p and ITGA3 in colorectal cancer (CRC) have rarely been reported. The aim of the present study was to explore the roles of miR‑199a‑5p and ITGA3 in CRC. Immunohistochemistry staining and western blotting were applied to detect the protein expression of ITGA3 in CRC tissues and cells. Reverse transcription‑quantitative PCR was performed to investigate the expression of miR‑199a‑5p and ITGA3 mRNA. HCT‑116 cells were transfected with miR‑199a‑5p mimics, mimics control, short hairpin RNA targeting ITGA3, or pcDNA‑ITGA3 for the functional experiments. Dual luciferase reporter assay was applied to confirm whether miR‑199a‑5p targeted the 3' untranslated region (3'UTR) of ITGA3. The MTT, Transwell and wound healing assays were used to evaluate the proliferation, invasion and migration of CRC cells. Immunofluorescence assay was used to monitor the epithelial‑mesenchymal transition (EMT) biomarker expression. The results demonstrated downregulation of miR‑199a‑5p and upregulation of ITGA3 in CRC tissues and cell lines. miR‑199a‑5p mimics and knockdown of ITGA3 suppressed the proliferation, invasion and migration of CRC cells. Bioinformatics analysis and luciferase reporter assay indicated that miR‑199a‑5p targeted the 3'UTR of the ITGA3 transcript, and overexpression of ITGA3 reversed the tumor‑suppressive effects of miR‑199a‑5p elevation. In addition, the immunofluorescence assay suggested that miR‑199a‑5p mimics suppressed the EMT of CRC cells, whereas the overexpression of ITGA3 restored this effect. In conclusion, miR‑199a‑5p may act as a tumor suppressor by targeting and negatively regulating ITGA3 in CRC.

Long non‑coding RNA (lncRNA) ZNFX1 antisense RNA 1 (ZFAS1) is upregulated in acute myocardial infarction; however, the role of ZFAS1 in myocardial ischemia/reperfusion (I/R) injury remains unknown. The present study aimed to detect microRNA (miR)‑590‑3p expression levels in cardiomyocytes subjected to I/R, and to investigate the effects of ZFAS1 on myocardial I/R injury. An in vitro model of I/R injury was established using rat H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R). It was demonstrated that ZFAS1 was upregulated and miR‑590‑3p was downregulated in the in vitro model of cardiac I/R injury. Western blotting results indicated that the protein expression levels of p50, tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6, Bax and cleaved caspase‑3 were upregulated, and the expression levels of Bcl‑2 and pro‑caspase‑3 were downregulated. Flow cytometry results revealed that downregulation of ZFAS1 reduced H/R‑induced apoptosis in H9c2 cells. In addition, downregulation of ZFAS1 significantly increased the expression of miR‑590‑3p, and p50 was identified as a target gene of miR‑590‑3p. Furthermore, with 12 h of hypoxia followed by 2 h of reoxygenation in H9c2 cells, ZFAS1 knockdown increased the expression levels of miR‑590‑3p, Bax and cleaved‑caspase‑3, and decreased the expression levels of Bcl‑2 and pro‑caspase‑3. It was also found that the miR‑590‑3p‑mimic transfection increased the expression levels of Bax and cleaved‑caspase‑3, and decreased the protein expression levels of p50, TNF‑α, IL‑6, Bcl‑2 and pro‑caspase‑3. In addition, TNF‑α treatment induced apoptosis of H9c2 cells, and the changes in Bax, Bcl‑2, cleaved‑caspase‑3 and pro‑caspase‑3 expression levels in a dose‑dependent manner. Collectively, the present results suggested that ZFAS1 was upregulated in H9c2 cells subjected to I/R injury, and that ZFAS1 knockdown protected against I/R‑induced myocardial cell apoptosis by directly interacting with miR‑590‑3p, via the NF‑κB pathway.

Nephrotic syndrome (NS) is one of the most common causes of chronic kidney disease in the pediatric population. Hyperlipidemia is one of the main features of NS. The present study investigated the role of CXC motif chemokine ligand 16 (CXCL16) and ADAM metallopeptidase domain 10 (ADAM10) in oxidized low‑density lipoprotein (oxLDL)‑stimualted podocytes and the underlying mechanisms. CXCL16 and ADAM10 expression levels in oxLDL‑treated podocytes were measured via reverse transcription‑quantitative PCR and western blotting. Cell migration assays were conducted to assess the migration of oxLDL‑treated podocytes. CXCL16 or ADAM10 overexpression and knockdown assays were conducted. The results indicated that oxLDL stimulation increased ADAM10 and CXCL16 expression levels, and enhanced podocyte migration compared with the control group. Moreover, CXCL16 and ADAM10 overexpression significantly increased podocyte migration and the expression of actinin‑α4 (ACTN4) compared with the control groups. By contrast, CXCL16 and ADAM10 knockdown significantly reduced podocyte migration and the expression of ACTN4 compared with the control groups. The results suggested that oxLDL promoted podocyte migration by regulating CXCL16 and ADAM10 expression, as well as by modulating the actin cytoskeleton. Therefore, CXCL16 and ADAM10 may serve as novel therapeutic targets for primary nephrotic syndrome in children.

The incidence of intervertebral disc degeneration (IDD) is increasing, especially among elderly individuals. The present study aimed to investigate the effects of the NF‑κB/p53 signaling pathway on IDD and its regulatory effect on associated cytokines. In the present study, human nucleus pulposus cells were isolated from patients with thoracic‑lumbar fractures and patients with IDD to observe cellular morphology and detect phosphorylated (p)‑p65/p53 expression levels. The locality and expression levels of p65 in interleukin (IL)‑1β‑stimulated nucleus pulposus cells, with or without the addition of ammonium pyrrolidinedithiocarbamate (PDTC; a NF‑κB signaling pathway‑specific blocker), were measured. Furthermore, the effects of IL‑1β stimulation on the protein and gene expression levels of IDD‑related cytokines were determined following p53 knockdown and inhibition of the NF‑κB signaling pathway. The results suggested that p‑p65 and p53 expression was significantly increased in IDD cells compared with normal nucleus pulposus cells. Moreover, nucleus pulposus cells isolated from patients with IDD contained less cytoplasm compared with normal nucleus pulposus cells, and p65 expression levels were higher in the cytoplasm than the nucleus of IL‑1β‑stimulated PDTC‑treated healthy nucleus pulposus cells. Moreover, the p53 expression levels were significantly decreased following transfection with sip53. PDTC treatment and p53 knockdown significantly decreased matrix metallopeptidase (MMP)‑3, MMP‑13, metallopeptidases with thrombospondin type 1 motif (ADAMTS)‑4 and ADAMTS‑5 expression levels, and increased aggrecan and collagen type II expression levels in IL‑1β‑stimulated cells. The present study indicated that activation of the NF‑κB/p53 signaling pathway might be related to the occurrence of IDD; therefore, the NF‑κB/p53 signaling pathway may serve as a therapeutic target for IDD.

Local transplantation of epidermal stem cells (ESCs) exerts a therapeutic effect on burn wounds. However, cell viability can impede their clinical application. HOX antisense intergenic RNA (HOTAIR) is involved in regulating adult tissue stem cells, as well as in developmental patterning and pluripotency. However, little is known about its role in regulating ESCs. The present study was performed to investigate the effects of HOTAIR in the modulation of ESCs and wound repair. Firstly, reverse transcription‑quantitative PCR was used to detect the relative expression of HOTAIR during burn wound healing in mice to determine whether HOTAIR is associated with wound healing. Subsequently, ESCs derived from mouse skin were transfected with a lentiviral vector to overexpress or knockdown HOTAIR. The effects of HOTAIR on cell proliferation and differentiation were measured by 5‑bromodeoxyuridine and MTT assays, and by assessing NANOG mRNA expression. Lastly, mice with burns were administered a subcutaneous injection of HOTAIR‑overexpressing ESCs. Images were captured and histological analyses were performed to evaluate wound healing. The results revealed that the expression of HOTAIR gradually increased and peaked at day 7 post‑burn and maintained at relatively high levels until day 14 post‑burn during wound healing. Furthermore, overexpression of HOTAIR promoted ESC proliferation and maintained the stem cell state in vitro. By contrast, suppression of HOTAIR inhibited cell proliferation and cell stemness. It was also identified that HOTIR‑overexpressing ESCs accelerated re‑epithelialization and facilitated burn wound repair. In conclusion, the present findings confirmed an essential role of HOTAIR in the regulation of ESC proliferation and stemness. Therefore, targeting HOTAIR in ESCs may be a potentially promising therapy for burn wound healing.

Postoperative cognitive dysfunction (POCD) is a prevalent neurocognitive disorder following surgery and anesthesia, particularly in elderly patients. Isoflurane is a widely used anesthetic agent, which is associated with the development of POCD; however, the precise mechanisms remain unclear. In the present study, aged rats were exposed to 2% isoflurane to establish a POCD model. The expression of PYRIN‑containing Apaf1‑like protein 1 (PYPAF1) was knocked down using a lentivirus containing specific short hairpin RNA. Subsequently, the spatial learning ability of rats was assessed using the Morris water maze. In addition, mRNA and protein expression levels were detected using reverse transcription‑quantitative PCR and western blot analysis, respectively. Immunofluorescence double staining was also used to determine the expression of PYPAF1 and Iba‑1 in the hippocampus. Neural apoptosis was observed using TUNEL‑NeuN double staining. The results revealed that isoflurane exposure impaired the spatial learning ability of rats, while PYPAF1 knockdown alleviated cognitive impairment. In addition, isoflurane exposure induced activation of the PYPAF1 inflammasome, as evidenced by elevated expression of PYPAF1 and apoptosis‑associated speck‑like protein containing a caspase recruitment domain, while silencing of PYPAF1 partially reversed this effect. Furthermore, isoflurane exposure promoted the activation of microglia and caspase‑1, and the secretion of interleukin (IL)‑1β and IL‑18, all of which were alleviated following PYPAF1 silencing. Moreover, isoflurane exposure induced neuronal apoptosis, elevated the levels of Bax and cleaved caspase‑3, and inhibited the expression of Bcl‑2; all of these effects were partially abrogated following PYPAF1 silencing. In conclusion, the results of the present study indicated that PYPAF1 silencing partially abolished isoflurane‑induced cognitive impairment, neuroinflammation and neuronal apoptosis. Therefore, PYPAF1 may be a potential therapeutic target for treatment of POCD.

The revascularization of blood vessels after myocardial infarction can lead to serious myocardial damage. Previous studies showed that radioprotective 105 kDa protein (RP105) is a specific negative regulator of myocardial ischemia reperfusion injury (MIRI). RP105 can modulate the Toll-like receptor (TLR)2/TLR4 signaling pathways. However, the synergistic effect of TLR2/4 regulated by RP105 during MIRI requires further investigation. To determine this effect, a MIRI model was established in rats in the present study. The expression of RP105 was depleted by transfecting RP105-siRNA and then detected using western blotting. Furthermore, the myocardium tissue was stained with the hematoxylin and eosin staining. Knockdown of RP105 promoted the activity of serum myocardial enzymes during MIRI and increased myocardial infarction. The present results indicated that knockdown of RP105 activated the TLR2/4 signaling pathway by modulating the myeloid differentiation primary response 88 and NF-κB signaling pathways. Furthermore, decreased expression of RP105 promoted myocardial cell apoptosis, which induced the damage of myocardial ischemic reperfusion. The present results suggested both TLR2 and TLR4 as key targets of RP105, thus RP105 may be a promising candidate to facilitate the development of novel therapeutic strategies for MIRI.

Curcumin is a naturally active phenolic compound extracted from the rhizome of the plant Curcuma longa, which has been demonstrated to serve as an anticancer drug in different types of cancer, including non‑small‑cell lung cancer (NSCLC). Accumulating evidence has suggested that curcumin may exert epigenetic regulatory effects on microRNAs (miRs). Therefore, the present study aimed to investigate the role of miR‑192‑5p, and the effects of curcumin, in NSCLC, alongside the underlying mechanisms. Human NSCLC cells, A427 and A549, were treated with curcumin, and the expression levels of miR‑192‑5p and c‑Myc were detected using reverse transcription‑quantitative PCR and western blotting. Cellular proliferation was analyzed using Cell Counting Kit‑8 assays and cell viability was determined using a MTT assay. Additionally, the migratory and invasive abilities of cells were analyzed using Transwell and Matrigel assays, respectively. The binding sites between miR‑192‑5p and c‑Myc were predicted using TargetScanHuman software, and confirmed using a dual‑luciferase reporter assay and RNA immunoprecipitation. Finally, the Wnt pathway regulator, β‑catenin, and cyclin D1 expression levels were determined using western blotting. Curcumin treatment inhibited NSCLC cell proliferation, migration, invasion and viability in a dose‑dependent manner, in addition to promoting a dose‑dependent increase in the expression levels of miR‑192‑5p and a reduction in c‑Myc expression levels. Notably, the genetic knockdown of miR‑192‑5p blocked the inhibitory effects of curcumin on NSCLC progression and instead promoted NSCLC progression, which was observed to be partially reversed by c‑Myc silencing; thus, c‑Myc was suggested to be a direct target gene of miR‑192‑5p as demonstrated by the TargetScanHuman database, dual‑lucierase and RIP assay results. In addition, the curcumin‑induced decreased expression levels of β‑catenin, cyclin D1 and c‑Myc were rescued following the genetic knockdown of miR‑192‑5p. In conclusion, these findings suggested that the upregulation of miR‑192‑5p may underlie the inhibitory effects of curcumin on NSCLC cells through targeting c‑Myc and inactivating the Wnt/β‑catenin signaling pathway.

The present study aimed to investigate the effect of the long non-coding RNA antisense non-coding RNA in the INK4 locus (lnc-ANRIL) knockdown on apoptosis, neurite outgrowth and inflammation based on a PC12 cellular Alzheimer's disease (AD) model. A cellular AD model was constructed by treating nerve growth factor stimulated PC12 cells with amyloid β (Aβ) 1–42 and then control knockdown plasmid and lnc-ANRIL knockdown plasmid were transfected in the PC12 cellular AD model as the KD- negative control (NC) group or the AD-ANRIL group respectively. Apoptosis, neurite outgrowth, pro-inflammatory cytokines and microRNA (miR)-125a were assessed. Rescue experiments were conducted by transfecting lnc-ANRIL knockdown plasmid and lnc-ANRIL knockdown plasmid and miR-125a inhibitor in the PC12 cellular AD model as the KD-ANRIL group or KD-ANRIL + KD-miR-125a group respectively. Following transfection, cell apoptosis deccreased while neurite outgrowth increased in the KD-ANRIL group compared with the KD-NC group (all P

Resveratrol (RSV) and long non‑coding RNAs (lncRNAs) play a role in the treatment of diabetes; however, the mechanism by which resveratrol regulates insulin resistance via lncRNAs is currently unknown. The present study aimed to determine the lncRNA expression level profile in mice following resveratrol treatment to improve insulin resistance using high‑throughput sequencing technology. C57BL/6J mice were fed a high‑fat diet for 8 weeks to develop an insulin resistance model, followed by treatment with or without RSV for 6 weeks before high‑throughput sequencing. Following RSV treatment, 28 and 30 lncRNAs were up‑ and downregulated, respectively; eight lncRNAs were randomly selected and evaluated using reverse transcription‑quantitative PCR, which showed results consistent with the sequencing analysis. Pathway analysis demonstrated that the insulin signaling pathway enrichment score was the highest, and identified two lncRNAs, NONMMUT058999.2 and NONMMUT051901.2, consistent with the protein‑encoding genes SOCS3 and G6PC, respectively. Similar expression level patterns were observed for SOCS3 and G6PC, suggesting that RSV improves insulin resistance by modulating lncRNAs. RSV decreased the expression levels of SOCS3, FOXO1, G6PC and PEPCK in mice. The same results were observed following knockdown of NONMMUT058999.2 in cells. The present study provides a new biomarker or intervention target for RSV in the treatment of diabetes, and a new perspective for understanding the hypoglycemic mechanism of RSV.

Endoplasmic reticulum (ER) oxidase 1α (ERO1α) is a glycosylated flavoenzyme that is located on the luminal side of the ER membrane, which serves an important role in catalyzing the formation of protein disulfide bonds and ER redox homeostasis. However, the role of ERO1α in myocardial hypoxia/reoxygenation (H/R) injury remains largely unknown. In the present study, ERO1α expression levels in H9C2 cardiomyocytes increased following H/R, reaching their highest levels following 3 h of hypoxia and 6 h of reoxygenation. In addition, H/R induced apoptosis, and significantly increased expression levels of ER stress (ERS) markers 78 kDa glucose‑regulated protein and C/EBP homologous protein. Moreover, the genetic knockdown of ERO1α using short hairpin RNA suppressed cell apoptosis, caspase‑3 activity, expression levels of cleaved caspase‑12 and cytochrome c in the cytoplasm. Overall, this suggested that ERO1α knockdown may protect against H/R injury. The ERS activator tunicamycin (TM) was used to counteract the ERO1α‑induced reduction in ERS; however, the percentage of apoptotic cells and the level of mitochondrial damage did not change. In conclusion, the results from the present study suggested that ERO1α knockdown may protect H9C2 cardiomyocytes from H/R injury through inhibiting intracellular ROS production and increasing intracellular levels of Ca2+, suggesting that ERO1α may serve an important role in H/R.

Hypopharyngeal squamous cell carcinoma (HSCC) is a malignant tumor found in the head and neck region. Lactate receptor 1, also known as G protein‑coupled receptor81 (GPR81), has been reported to play a vital role in cancer growth and metabolism. However, the function of GPR81 in HSCC remains largely unknown. The present study investigated the effect of GPR81 on cell survival and GPR81‑mediated energy metabolism under cisplatin treatment in HSCC. GPR81 knockdown reduced the proliferation and invasion of the human HSCC cell line FaDu. Furthermore, GPR81 silencing combined with cisplatin treatment increased the expression of translocase of outer mitochondrial membrane 20 at the mRNA and protein levels (P

Interleukin (IL)-1β is a key promotor in the pathogenesis of temporomandibular joint osteoarthritis. Differentiation of stem cells to cartilage is a crucial repair mechanism of articular cartilage damage, and IL-1β has been reported to impede the differentiation by upregulating the secretion of IL-6, an important inflammatory factor. Long non-coding RNAs (lncRNAs) regulate a number of physiological and pathological processes, but whether lncRNA AK094629 contributes to the IL-1β mediated induction of inflammation remains unclear. Therefore, the aim of the present study was to investigate the effect of AK094629 on IL-1β-induced IL-6 expression in synovial-derived mesenchymal stem cells (SMSCs) of the temporomandibular joints. The results of the present study demonstrated that the expression of AK094629 in the synovial tissue of patients with osteoarthritis was positively correlated with IL-1β. In addition, IL-1β upregulated the expression of AK094629 in the SMSCs in vitro, and AK094629 knockdown inhibited the IL-1β mediated upregulation of IL-6. The present study also demonstrated that AK094629 knockdown downregulated the expression of the mitogen-activated protein kinase kinase kinase 4 (MAP3K4), which is upregulated by IL-1β, whereas knockdown of MAP3K4 did not affect the expression of AK094629, but reversed the upregulation of IL-6 in SMSCs. In conclusion, AK094629 knockdown attenuated the expression of IL-1β-regulated IL-6 in the SMSCs of the temporomandibular joint by inhibiting MAP3K4. Therefore, AK094629 may be a potential novel therapeutic target for the treatment of temporomandibular joint osteoarthritis.

Lung cancer is a devastating cancer with high morbidity and mortality. Ubiquitin-specific protease (USP) is a type of deubiquitinating enzyme (DUB) that has been implicated in numerous cancers, including colorectal, myeloma and breast. In the present study, the expression of USP51 was determined in the lung cancer cell line A549 and cisplatin (also known as DDP)-resistant lung cancer strain A549/DDP. The expression of zinc-finger E-box binding homeobox 1 (ZEB1), a transcriptional repressor, was also examined. The effects of USP51 knockdown or overexpression on proliferation and apoptosis, as well as the impact of ZEB1 overexpression and USP51 interference on apoptosis and ubiquitination were then assessed. Notably, increased expression of USP51 and ZEB1 in A549/DDP cells was observed, and treatment with DDP significantly inhibited proliferation in A549/DDP cells. In addition, knockdown of USP51 in A549/DDP cells significantly induced apoptosis, decreased ZEB1 expression and increased cleaved poly ADP-ribose polymerase 1 (PARP1) and cleaved caspase-3 levels. Consistently, USP51 overexpression in A549 cells displayed the opposite effects and potently attenuated DDP-induced apoptosis. Notably, overexpression of ZEB1 in A549/DDP cells potently attenuated the effects of USP51 knockdown on apoptosis, and co-IP experiments further demonstrated interaction between USP51 and ZEB. Lastly, knockdown of USP51 promoted ZEB1 ubiquitination, leading to ZEB1 degradation. Collectively, the present findings demonstrated that USP51 inhibition attenuated DDP resistance in A549/DDP cells via ubiquitin-mediated degradation of ZEB1. Hence, targeting USP51 may serve as a novel therapeutic target for DDP resistance in lung cancer.

Posterior capsular opacification (PCO) is the main complication following cataract surgery. The proliferation of the residual lens epithelial cells (LECs) serves an important role in PCO formation. The authors' previous study revealed that vitamin C inhibited the proliferation of human LECs by increasing the rapid degradation of hypoxia-inducible factor-1 (HIF-1α), and hence inhibited the expression of vascular endothelial growth factor (VEGF). The present study aimed to further investigate the mechanisms underlying the effects of vitamin C on the expression levels of VEGF. The present study demonstrated that the HIF-1 inhibitor BAY 87–2243 significantly inhibited the cell proliferation and the expression levels of VEGF in LECs through the use of colony formation, western blotting and ELISA assays. Moreover, it was revealed that vitamin C could further inhibit the cell proliferation and the expression levels of VEGF in LECs following the cotreatment with the HIF-1 inhibitor. The proline hydroxylation of HIF-1α by prolyl hydroxylases (PHDs) was previously discovered to be responsible for the rapid degradation of HIF-1α. Thus, the present study subsequently used three PHD inhibitors to investigate their effects on the expression levels of VEGF; it was found that the PHD2 specific inhibitor increased the expression levels of VEGF to the greatest extent. Moreover, the genetic knockdown of PHD2 by lentiviral transfection also significantly increased the expression levels of VEGF, whereas the PHD2 specific inhibitor did not alter the expression levels of VEGF in the PHD2 knockdown LECs. AKT kinase activity is an important mediator known to upregulate VEGF expression. Using an immunoprecipitation assay to isolate endogenous AKT, it was demonstrated that AKT was prolyl hydroxylated by PHD2, which inhibited its activity. It was also revealed that vitamin C enhanced the proline-hydroxylation and inhibited the activity of AKT. Furthermore, an AKT inhibitor increased the effects of vitamin C on the expression levels of VEGF. However, the AKT inhibitor did not affect the expression levels of glucose transporter 1, which is a HIF-1α target gene. In conclusion, the findings of the present study suggested that vitamin C may inhibit the expression levels of VEGF via HIF-1α-dependent and AKT-dependent pathways in LECs.

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)‑induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription‑quantitative PCR results indicated that inhibition of miR‑125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR‑125a abrogated this effect. Furthermore, dual‑luciferase reporter assay results identified that 3‑hydroxy‑3-methyglutaryl‑coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR‑125a. Moreover, HMGCR knockdown, similarly to miR‑125a overexpression, suppressed HG‑induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin‑induced diabetes mellitus, it was demonstrated that miR‑125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG‑induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR‑125a mimic. Therefore, the present results suggest that decreased miR‑125a expression contributed to HG‑induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR‑125a‑mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis.

Atherosclerosis (AS), a major cause of cardiovascular disease, has developed into a serious challenge to the health system. The long non‑coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is associated with the pathogenesis of AS. However, whether MALAT1 can affect cholesterol accumulation in macrophages during AS progression, and the potential molecular mechanism involved in this progression have not been elucidated. In the present study, the mRNA expression level of MALAT1 was measured using reverse transcription‑quantitative PCR (RT‑qPCR) and the protein expression level was detected via western blot analysis. Oil Red O staining was used for detecting lipid accumulation in macrophages. Bioinformatics, dual‑luciferase reporter and RT‑qPCR assays were used to investigate the relationship between MALAT1 and the microRNA (miR)‑17‑5p/ATP‑binding cassette transporter A1 (ABCA1) axis. The present results suggested that the MALAT1 expression level was significantly decreased in patients with AS and in oxidized low‑density lipoprotein (ox‑LDL)‑stimulated macrophages. Knockdown of MALAT1 increased ox‑LDL uptake, lipid accumulation and the total cholesterol (T‑CHO) level in ox‑LDL‑induced macrophages. In addition, MALAT1 inhibition significantly decreased the mRNA and protein expression levels of scavenger receptor (SR) class B member 1, apolipoprotein E (ApoE) and ABCA1. However, MALAT1 increased the expression level of SR class A. Subsequently, the present study investigated whether MALAT1 could target miR‑17‑5p to regulate the expression level of ABCA1, which is involved in cholesterol efflux from macrophages. The present results suggested that inhibition of miR‑17‑5p reversed the effects of MALAT1 knockdown on T‑CHO content, and protein expression levels of ApoE and ABCA1 in ox‑LDL‑stimulated macrophages. In summary, knockdown of MALAT1 may promote cholesterol accumulation by regulating the miR‑17‑5p/ABCA1 axis in ox‑LDL‑induced THP‑1 macrophages.

Osteosarcoma (OS) is a primary malignant tumor that occurs in bone, and mainly affects children and adolescents. C‑type lectin domain family 3 member A (CLEC3A) is a member of the C‑type lectin superfamily, which regulates various biological functions of cells. The present study aimed to identify the effects and related mechanisms of CLEC3A in the proliferation and chemosensitivity of OS cells. The expression of CLEC3A in OS was analyzed using the Gene Expression Omnibus data profile GSE99671, and its expression in OS samples was verified using reverse transcription‑quantitative PCR (RT‑qPCR) and immunohistochemical staining. The relationship between the expression of CLEC3A and clinical traits in patients with OS was also analyzed, including age, tumor size, TNM stage and lymph node metastasis. Cell Counting Kit‑8 assays, colony formation assays and cell cycle distribution analysis were used to determine the roles of CLEC3A in the proliferation and chemosensitivity of OS cells. Finally, RT‑qPCR and western blotting were used to demonstrate the relationship between CLEC3A and the AKT1/mTOR/hypoxia‑inducible factor 1‑α (HIF1α) pathway. Both the mRNA and protein expression levels of CLEC3A were increased in OS tissues compared with adjacent non‑tumor tissues, and this was positively associated with TNM stage and lymph node metastasis. The genetic knockdown of CLEC3A with small interfering RNA decreased OS cell proliferation and colony formation, and induced G1 phase arrest, whereas the overexpression of CLEC3A increased OS cell proliferation and colony formation, and alleviated G1 phase arrest. The suppression of CLEC3A also promoted enhanced the chemosensitivity of OS cells to doxorubicin (DOX) and cisplatin (CDDP); it also inhibited the expression of AKT1, mTOR and HIF1α, further to the nuclear localization of HIF1α, and HIF1α target gene expression levels, including VEGF, GLUT1 and MCL1 were also decreased. Furthermore, treatment with the AKT activator SC79 blocked the inhibitory effects of CLEC3A silencing in OS cells. In conclusion, these findings suggested that CLEC3A may function as an oncogene in OS, and that the suppression of CLEC3A may inhibit OS cell proliferation and promote chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway.

Receptor interacting protein kinase 4 (RIPK4) is a serine/threonine kinase that plays an important role in the regulation of cell proliferation, invasion and metastasis in several malignancies; however, its clinical significance and biological function in osteosarcoma (OS) remains unknown. In the present study, the RIPK4 expression level was significantly upregulated in OS tissues and cell lines. High RIPK4 expression was positively associated with larger sized tumors, advanced Enneking stage and poor prognosis in patients with OS. Furthermore, the results revealed that RIPK4 knockdown in the OS cell lines MG‑63 and U2OS reduced cell migration and invasion via the inhibition of epithelial‑mesenchymal transition (EMT) process, whereby E‑cadherin expression was increased and N‑cadherin and vimentin expression decreased. Mechanistically, RIPK4 knockdown inhibited EMT by inactivating the Wnt/β‑catenin signaling pathway. These findings suggest that RIPK4 may be a novel potential therapeutic target for the treatment of metastases in patients with OS.

Several studies have indicated that dysregulation of long non‑coding RNAs (lncRNAs) participates in the initiation and progression of cancer. The lncRNA MIR4435‑2HG was previously reported to act as an oncogene in human cancer, including liver cancer. However, its role in the pathogenesis in liver cancer is largely unclear. The present study aimed to reveal the molecular mechanism by which MIR4435‑2HG regulates liver cancer. The expression levels of MIR4435‑2HG in liver cancer and adjacent normal tissues were analyzed using The Cancer Genome Atlas database. MIR4435‑2HG expression was validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in cancer cells in vitro. The target genes of MIR4435‑2HG were predicted using bioinformatics analysis. Interactions between miR‑136‑5p, MIR4435‑2HG and B3GNT5 were detected using luciferase reporter assays, and their effects on cell viability, migration and invasion were assessed using Cell Counting Kit‑8, wound healing and Transwell assays. The effects of miR‑136‑5p and MIR4435‑2HG on B3GNT5 expression were confirmed by western blot analysis. The results revealed that MIR4435‑2HG expression was upregulated in primary liver cancer and liver cancer cell lines, and was positively associated with advanced tumor stage, metastasis and poor prognosis in patients with liver cancer. Knockdown of MIR4435‑2HG significantly inhibited the proliferation, migration and invasion of liver cancer cells. Furthermore, miR‑136‑5p was determined to be a direct target of MIR4435‑2HG and suppressed MIR4435‑2HG expression by binding with the seed region of the 3'‑UTR of MIR4435‑2HG in liver cancer cells. Functional studies showed that the inhibitory effects of MIR4435‑2HG knockdown on cell proliferation, migration and invasion were significantly rescued by inhibiting miR‑136‑5p. Furthermore, the target gene, B3GNT5, of miR‑136‑5p was confirmed by bioinformatics analysis and RT‑qPCR. In addition, B3GNT5 expression was regulated by the MIR4435‑2HG/miR‑136‑5p axis. In conclusion, the present study indicated that MIR4435‑2HG facilitated the progression of liver cancer via the MIR4435‑2HG/miR‑136‑5p/B3GNT5 axis, which demonstrated that MIR4435‑2HG may be a potential biomarker for the prognosis and treatment of liver cancer.

MicroRNAs (miRs) act as important regulators during the development and progression of human cancer; however, the regulatory mechanism of miR-663 in nasopharyngeal carcinoma (NPC) remains unclear. The present study demonstrated that serum miR‑663 levels were significantly increased in patients with NPC compared with healthy controls. In addition, the serum levels of miR‑663 were associated with the grade, lymph node metastasis and clinical stage of NPC. The expression of miR‑663 was increased in NPC C666‑1 cells, compared with normal nasopharyngeal epithelial NP69 cells. The knockdown of miR‑663 markedly decreased the proliferation of C666‑1 cells through the induction of cell cycle arrest at the G1 stage. Cyclin‑dependent kinase inhibitor 2A (CDKN2A) was hypothesized to be a putative target of miR‑663. Further investigation confirmed that miR‑663 was able to directly bind to the 3' untranslated region of CDKN2A mRNA, and to negatively regulate CDKN2A protein expression in C666‑1 cells. Inhibition of CDKN2A expression attenuated the suppressive effects of miR‑663 knockdown on the proliferation and cell cycle progression of C666‑1 cells. In addition, it was observed that the mRNA and protein levels of CDKN2A were decreased in C666‑1 cells compared with NP69 cells. In conclusion, the results of the present study demonstrated that miR‑663 promoted the proliferation and cell cycle progression of NPC cells by directly targeting CDKN2A, suggesting that miR‑663 may become a potential therapeutic target for the treatment of NPC.

The cellular resistance of tumors is a major obstacle for successful tumor therapy. Cluster of differentiation (CD)133 plays an important role in the regulation of drug resistance in gastric and colon cancers. However, its effect on chemotherapeutic sensitivity in adenoid cystic carcinoma (ACC) has not been fully explored. The present study discussed the specific role of CD133 in ACC drug-resistant sensitive cells. KOA-1 cells were treated with 5-fluorouracil (5-FU) and pingyangmycin (PYM) to form drug-resistant cell lines. A Cell Counting Kit-8 assay was used to detect the cell survival rate. Cell invasion was measured using a Transwell assay. The expression levels of CD133 were detected by reverse transcription-quantitative (RT-q) PCR. The expression levels of drug-resistant mRNAs and proteins were detected by RT-qPCR and immunofluorescence analyses, respectively. The CD133 were inhibited by small interfering RNA technology. The survival rate and invasive ability of KOA-1 cells were increased following the induction of drug resistance. The expression levels of CD133, multidrug resistance protein (MDR)1 and multidrug resistance-associated protein (MRP)1 were significantly increased in drug-resistant cell lines. Knockdown of CD133 expression in the resistant cell lines, KOA-1/5-FU and KOA-1/PYM, decreased the survival rate and invasive ability. The expression levels of MDR1 and MRP1 were also significantly decreased. Knockdown of CD133 expression in ACC drug-resistant cells could inhibit the viability and invasion of tumors and enhance the sensitivity of drug-resistant cells to chemotherapeutic drugs.

According to emerging evidence, long non-coding RNAs (lncRNAs) play critical roles in diabetes. The aim of the present study was to investigate the role and mechanism of X-inactive specific transcript (XIST) in cell proliferation, migration and apoptosis in diabetic cataracts (DC). SRA01/04 lens epithelial cells were treated with high glucose (HG). The levels of XIST, microRNA (miR)-34a and SMAD family member 2 (SMAD2) were examined via reverse transcription-quantitative PCR. MTT, Transwell, wound healing and TUNEL assays were performed to examine cell proliferation, invasion, migration and apoptosis, respectively. The interaction between miR-34a and XIST or SMAD2 was verified by luciferase reporter assay. It was found that the expression of XIST was increased and that of miR-34a was decreased in DC tissues and HG-treated SRA01/04 cells. XIST knockdown or miR-34a overexpression attenuated cell proliferation and migration, and induced apoptosis in HG-treated SRA01/04 cells. XIST targeted miR-34a and regulated DC progression through miR-34a. SMAD2 was identified as a target gene of miR-34a and was positively modulated by XIST. XIST knockdown inhibited cell proliferation and migration, and accelerated apoptosis in HG-stimulated SRA01/04 cells, and these effects were abrogated by SMAD2 overexpression. In conclusion, XIST promoted cell proliferation, migration and invasion, and inhibited apoptosis, through the miR-34a/SMAD2 axis in DC.

To investigate the role of NEAT1 and the microRNA (miR)-377/fibroblast growth factor receptor 1 (FGFR1) axis in cervical cancer (CC), the expression levels of NEAT1, FGFR1 and miR-377 were detected in CC tissues and cell lines. NEAT1 or FGFR1 was knocked down by transfection with short hairpin RNA (sh)-NEAT1 or sh-FGFR1, and miR-377 was overexpressed by transfection with miR-377 mimics in HeLa and C33A cells. Cell viability and migration were measured using MTT and Transwell assays, respectively. Cell apoptosis was determined by flow cytometry. A dual luciferase reporter assay was performed to confirm the presence of binding sites between miR-377 and FGFR1. The results revealed that the expression levels of NEAT1 and FGFR1 were significantly elevated, whereas miR-377 expression was markedly decreased in CC tissues and cell lines. In HeLa and C33A cells, after NEAT1 knockdown, miR-377 expression was increased, cell viability and migration were inhibited, and apoptosis was induced. Similarly, silencing FGFR1 inhibited cell viability and migration, and induced apoptosis of HeLa and C33A cells. A dual luciferase reporter gene assay verified a targeting relationship between NEAT1 and miR-377. Inhibition of miR-377 or overexpression of FGFR1 reversed the effects of NEAT1 knockdown on cell function in HeLa and C33A cells. Moreover, a dual luciferase reporter assay confirmed that FGFR1 was a direct target of miR-377. In conclusion, suppression of NEAT1 inhibited cell viability and migration, and promoted apoptosis of CC cells, and these effects were achieved through regulation of the miR-377/FGFR1 axis.

As a member of the long non-coding (lnc)RNA family, lncRNA maternally expressed 8, small nucleolar RNA host gene (MEG8), has been reported to serve an oncogenic role in several types of malignancies, including hepatocellular carcinoma, non-small cell lung cancer and pancreatic cancer. The current study aimed to investigate the effect of the knockdown of MEG8 on human hemangioma endothelial cell (HemEC) proliferation, apoptosis and invasion, in addition to determining the underlying molecular mechanism. The knockdown of lncRNA MEG8 was achieved by transfecting lncRNA MEG8 small interfering (si)RNA into HemECs, while the combined knockdown of lncRNA MEG8 knockdown and microRNA (miR)-203 was established by co-transfecting lncRNA MEG8 siRNA and a miR-203 inhibitor into HemECs. The cell proliferation, apoptosis and invasion and the expression levels of miR-34a, miR-200b, miR-200b and Notch signaling pathway-related factors were detected via CCK-8 Kit, flow cytometry, Transwell, reverse transcription-quantitative PCR and western blot assay, respectively. The knockdown of lncRNA MEG8 significantly inhibited proliferation (P0.05). Subsequent experiments revealed that miR-203 silencing exerted no significant effect on the expression levels of lncRNA MEG8 (P>0.05) in HemECs. In addition, miR-203 silencing increased cell proliferation (P

Intestinal mucositis is a common side effect of cancer chemotherapy and it limits the dose of chemotherapy given to a patient. Tripartite motif family (TRIM) proteins have been reported to be implicated in the regulation of cancer chemotherapy. The present study aimed to investigate the effect of TRIM9 on irinotecan‑induced intestinal mucositis in the rat intestinal epithelial cell line IEC‑6. The expression of several TRIMs, such as TRIM1, TRIM9, TRIM18, TRIM36, TRIM46 and TRIM67, was examined. After TRIM9 knockdown or overexpression by lentivirus infection, cell proliferation and apoptosis, epithelial barrier tight‑junction proteins, inflammatory cytokines, transepithelial electrical resistance (TEER) and FITC dextran were measured. Treatment with irinotecan significantly inhibited cell proliferation and induced cell apoptosis, TRIM9 expression, intestinal mucosal barrier impairment, the levels of inflammatory cytokines and P38 phosphorylation in IEC‑6 cells, while the expression levels of epithelial barrier tight‑junction protein ZO‑1 and Claudin‑4 were decreased. Knockdown of TRIM9 partly counteracted the effect of irinotecan treatment, and inhibition of P38 potently reversed the effect of TRIM9 overexpression in IEC‑6 cells. Moreover, co‑immunoprecipitation showed an interaction between TRIM9 and DUSP6 in IEC‑6 cells, and overexpression of DUSP6 notably counteracted the effect of TRIM9 overexpression. The results demonstrated that TRIM9 knockdown may benefit patients with intestinal mucositis by inhibiting inflammatory cytokine expression and repairing intestinal barrier functions, which was probably due to inhibition of the activation of the P38 pathway via targeting DUSP6.

Intervertebral disc degeneration (IDD) is a major cause of lower back pain. The high morbidity associated with this disease diminishes the quality of life of those who are affected. MicroRNAs (miRs) play crucial roles in various diseases, including IDD. However, the mechanism via which miR‑200c‑3p plays a role in the development of IDD remains unknown. The present study aimed to investigate the effect of miR‑200c‑3p on the progression of IDD and the underlying mechanism. The expression level of miR‑200c‑3p was evaluated in intervertebral disc tissues from patients with IDD. To construct the IDD cell model, the nucleus pulposus (NP) cells were treated with lipopolysaccharide (LPS) 24 h following transfection with miR‑200c‑3p mimic or inhibitor. A luciferase activity assay was performed, while reverse transcription‑quantitative PCR and western blotting were conducted to determine the RNA and protein expression levels, respectively. The expression level of miR‑200c‑3p in the intervertebral disc tissues of patients with IDD was lower than that of normal subjects. LPS treatment reduced the expression level of miR‑200c‑3p in NP cells. Moreover, miR‑200c‑3p mimic inhibited LPS‑induced NP cell apoptosis. It was found that miR‑200c‑3p attenuated inflammatory cytokine levels and extracellular matrix (ECM) degradation in NP cells. Furthermore, miR‑200c‑3p targeted Ras‑related protein 2C (RAP2C) in NP cells. RAP2C promoted apoptosis, inflammatory cytokine levels and ECM degradation by activating ERK signaling. Knockdown of RAP2C and inhibition of ERK signaling by SCH772984 partially reversed the proinflammatory effect of the miR‑200c‑3p inhibitor on LPS‑treated NP cells. Thus, miR‑200c‑3p inhibits NP cell apoptosis, inflammatory cytokine levels and ECM degradation in IDD by targeting RAP2C/ERK signaling.

Long non‑coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer (PCa) as competitive endogenous RNA. The present study aimed to investigate the molecular mech--anisms of lncRNA small nucleolar RNA host gene 16 (SNHG16) in the proliferation and metastasis of PCa cells. Cancer tissues and adjacent normal tissues were collected from 80 patients with PCa who did not receive any treatment. Reverse transcription‑quantitative PCR analysis was performed to detect the expression levels of SNHG16, hsa‑microRNA (miRNA/miR)‑373‑3p and transforming growth factor‑β receptor type 2 (TGF‑β‑R2), and Spearman's correlation coefficient analysis was performed to assess the correlations between these molecules. Furthermore, the effects of SNHG16 knockdown and overexpression on the biological functions of DU‑145 PCa cells and TGF‑β‑R2/SMAD signaling were analyzed. The dual‑luciferase reporter assay was performed to assess the associations between SNHG16 and miR‑373‑3p, and TGF‑β‑R2 and miR‑373‑3p, the effects of which were verified via rescue experiments. The results demonstrated that the expression levels of SNHG16 and TGF‑β‑R2 were significantly upregulated in PCa tissues, whereas miR‑373‑3p expression was significantly downregulated (P

Parkinson's disease (PD), a common multifactorial neurodegenerative disease, is characterized by irreversible loss of dopaminergic neurons in the substantia nigra. In-depth study of the pathogenesis of PD is of great importance. High-mobility group AT-hook 2 (HMGA2) has been proposed to be implicated with neuronal differentiation and impairment of cognitive function. However, whether HMGA2 plays a role in PD is rarely explored. In the present study, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD mice models and N-methyl-4- phenylpyridinium (MPP+)-treated SH-SY5Y cell models were established. Reverse transcription-quantitative PCR showed that HMGA2 displayed low levels in brain tissues of MPTP-treated mice and MPP+-treated SH-SY5Y cells. Moreover, HMGA2 overexpression suppressed SH-SY5Y cell apoptosis. Additionally, let-7b-5p bound with HMGA2 3′ untranslated region (UTR), and its expression was negatively correlated with HMGA2 level. Moreover, let-7b-5p presented high levels in brain tissues of PD mice and MPP+-treated SH-SY5Y cells, and knockdown of let-7b-5p inhibited SH-SY5Y cell apoptosis. Rescue assays illustrated that HMGA2 neutralized the promotive effects of let-7b-5p mimics on SH-SY5Y cell apoptosis. In conclusion, the present study demonstrated that let-7b-5p contributes to cell apoptosis in PD by targeting HMGA2, which offers a potential theoretical basis for the study of effective therapy in PD.

Allergic rhinitis (AR) is an IgE‑mediated upper airway disease with a high worldwide prevalence. MicroRNA (miR)‑205‑5p upregulation has been observed in AR; however, its role is poorly understood. The aim of the present study was to investigate the effect of miR‑205‑5p on AR‑associated inflammation. To establish an AR model, BALB/c mice were sensitized using an intraperitoneal injection of ovalbumin (OVA) on days 0, 7 and 14, followed by intranasal challenge with OVA on days 21‑27. A lentiviral sponge for miR‑205‑5p was used to downregulate miR‑205‑5p in vivo via intranasal administration on days 20‑26. Reverse transcription‑quantitative PCR revealed that miR‑205‑5p was upregulated in AR mice. Notably, miR‑205‑5p knockdown reduced the frequency of nose‑rubbing and sneezing, and attenuated pathological alterations in the nasal mucosa. The levels of total and OVA‑specific IgE, cytokines IL‑4, IL‑5 and IL‑13, and inflammatory cells, were decreased by miR‑205‑5p knockdown in AR mice. In addition, miR‑205‑5p knockdown inhibited nucleotide‑binding oligomerization domain‑like receptor family pyrin domain‑containing 3 (NLRP3) inflammasome activation by reducing the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, cleaved caspase‑1 and IL‑1β by western blot analysis. B‑cell lymphoma 6 (BCL6) was confirmed as a target of miR‑205‑5p by luciferase reporter assay. In conclusion, the present findings suggested that miR‑205‑5p knockdown may attenuate the inflammatory response in AR by targeting BCL6, which may be a potential therapeutic target for AR.

Long non-coding RNA (lncRNA) tumor protein translationally controlled 1 antisense RNA 1 (TPT1-AS1) serves as an oncogene in several tumors, including ovarian and cervical cancer. However, the functional role of TPT1-AS1 in liver cancer (LC) is not completely understood. The present study aimed to explore the role of TPT1-AS1 in LC. In this study, the reverse transcription-quantitative PCR results demonstrated that TPT1-AS1 expression was significantly upregulated in LC tissues and cell lines compared with adjacent paracancerous tissues and THLE-3 cells, respectively. Elevated TPT1-AS1 expression was significantly associated with TNM stage lymph node metastasis and poor prognosis in patients with LC, as determined via χ2 and Kaplan-Meier survival analyses. By constructing TPT1-AS1 knockdown LC cell lines (HepG2 and SNU-182), loss-of-function experiments, including Cell Counting Kit-8, colony formation, flow cytometry, wound healing and Transwell assays, were performed to explore the function role of TPT1-AS1 in LC in vitro. The results demonstrated that TPT1-AS1 knockdown inhibited LC cell proliferation, G1/S transition, migration and invasion compared with the small interfering RNA (si)-negative control (NC) group. Mechanistically, TPT1-AS1 knockdown markedly decreased CDK4, N-cadherin and Vimentin expression levels, but notably increased p21 and E-cadherin expression levels compared with the si-NC group. Therefore, the results of the present study suggested that TPT1-AS1 might serve as a promising therapeutic target for LC treatment.

HOXC10 and mitochondrial fission regulator 2 (MTFR2) have been reported to be abnormally expressed in multiple types of cancer tissues. However, the effects of HOXC10 and MTFR2 on colorectal cancer (CRC) remain poorly understood. Therefore, the present study aimed to investigate the expression of HOXC10 and MTFR2 in CRC tissues and cells, and analyze their effects on CRC cell proliferation, invasion and migration. Reverse transcription‑quantitative PCR and western blotting were used to detect the expression levels of MTFR2 and HOXC10 in tissues and cells. To investigate the association between MTFR2 and HOXC10, short hairpin RNA‑MTFR2 and overexpression vector‑HOXC10 were transfected into the cells, respectively. Furthermore, western blotting was performed to detect the expression levels of invasion‑associated proteins. The proliferation, clone formation, invasion and migration of colorectal cancer cells were in turn analyzed by the Cell Counting Kit‑8, clone formation, wound healing and Transwell assays. Japan Automotive Software Platform and Architecture software predicted the binding sites between HOXC10 and MTFR2, which was confirmed by the dual‑luciferase reporter assay and chromatin immunoprecipitation. The present study demonstrated that HOXC10 and MTFR2 mRNA and protein expression levels were significantly upregulated in CRC tissues and cells. MTFR2 knockdown significantly inhibited CRC cell proliferation, clone formation, invasion and migration. Furthermore, HOXC10 was shown to interact with MTFR2. HOXC10 overexpression was able to significantly reverse the inhibitory effects of MTFR2 knockdown on CRC cells. In conclusion, HOXC10 overexpression activated MTFR2 expression to enhance the proliferation, clone formation, invasion and migration of CRC cells.

Pancreatic cancer (PC) is a malignant tumor disease, whose molecular mechanism is not fully understood. Sodium channel epithelial 1α subunit (SCNN1A) serves an important role in tumor progression. The current study explored the role of homeobox D9 (HOXD9) and SCNN1A in the progression of PC. The expression of SCNN1A and HOXD9 in PC samples was predicted on online databases and detected in PC cell lines. The association between SCNN1A expression and PC prognosis was examined by the Gene Expression Profiling Interactive Analysis, The Cancer Genome Atlas and Genotype‑Tissue Expression databases and by a Kaplan‑Meier plotter. Subsequently, the biological effects of SCNN1A on PC cell growth, colony formation, migration and invasion were investigated through RNA interference and cell transfection. Next, the expression of E‑cadherin, N‑cadherin, Vimentin and Snail was detected by western blotting to discover whether HOXD9 dysregulation mediated PC metastasis. Binding sites of HOXD9 and SCNN1A promoters were predicted on JASPAR. Reverse transcription‑quantitative PCR and western blotting were used to detect the expression level of SCNN1A following interference and overexpression of HOXD9. Luciferase assay detected luciferase activity following interference with HOXD9 and the transcriptional activity of SCNN1A following binding site deletion. High expression of SCNN1A and HOXD9 in PC was predicted by online databases, signifying poor prognosis. The present study confirmed the above predictions in PC cell lines. Knockdown of SCNN1A and HOXD9 could effectively inhibit the proliferation, migration, invasion and epithelial‑mesenchymal transition of PC cells. Furthermore, HOXD9 activated SCNN1A transcription, forming a feedback regulatory loop. HOXD9 was demonstrated to activate SCNN1A and promote the malignant biological process of PC.

Circular RNAs (circRNAs) regulate gene expression by acting as a 'sponge' for microRNAs (miRs) and play crucial roles in tumorigenesis, including in bladder cancer (BC). circRNA‑baculoviral IAP repeat‑containing 6 (circ‑BIRC6) has been reported to participate in the pathogenesis of several cancer types. The present study aimed to elucidate the roles and potential mechanisms of circ‑BIRC6 in the progression of BC. circ‑BIRC6 expression levels in BC cell lines were determined using reverse transcription‑quantitative PCR. Following circ‑BIRC6 knockdown, cell proliferation, invasion and migration were detected using Cell Counting Kit‑8, colony formation, Transwell and wound healing assays, respectively. Western blotting was also conducted to evaluate the expression levels of X‑box binding protein 1 (XBP1) and epithelial‑mesenchymal transition (EMT)‑associated proteins. In addition, rescue experiments were performed using by transfecting a miR‑495‑3p inhibitor into T24 cells following circ‑BIRC6 knockdown. The interactions between circ‑BIRC6, miR‑495‑3p and XBP1 was verified using dual luciferase reporter assays. Moreover, T24 cells with circ‑BIRC6 knockdown and miR‑495‑3p inhibitor transfection were used for the tumor‑bearing experiment. Tumor growth was observed and Ki‑67 expression was determined using immunohistochemistry. The results demonstrated that circ‑BIRC6 expression was upregulated in BC cell lines. Moreover, circ‑BIRC6 knockdown notably attenuated the proliferation, invasion, migration and EMT of BC cells, which was blocked by the miR‑495‑3p inhibitor. It was also identified that circ‑BIRC6 sponged miR‑495‑3p to regulate XBP1 expression. In addition, results from the xenograft experiments indicated that the knockdown of circ‑BIRC6 and miR‑495‑3p expression significantly inhibited tumor growth. It was also found that the expression levels of XBP1, Ki‑67 and EMT‑associated proteins in tumor tissues of the co‑transfection group were markedly restored compared with the circ‑BIRC6 knockdown group. In conclusion, these findings demonstrated that circ‑BIRC6 knockdown suppressed BC tumorigenesis and progression via regulation of the miR‑495‑3p/XBP1 signaling axis, offering a promising therapeutic target for the treatment of BC.

Glioblastoma (GBM) is one of the most common and malignant types of primary cancer in the central nervous system; however, the clinical outcomes of patients with GBM remain poor. Circular RNAs (circRNAs) have been revealed to serve important roles in diverse biological processes, such as regulating cell proliferation, epithelial‑mesenchymal transition and tumor development. However, the underlying biological function of circRNA filamin A (circFLNA) and its potential role in GBM remain to be determined. The present study aimed to identify differentially expressed circRNAs in GBM. Reverse transcription‑quantitative PCR was used to analyze the expression levels of circFLNA. The results demonstrated that the expression levels of circFLNA were significantly upregulated in clinical GBM samples and GBM cells compared with adjacent healthy brain tissues and normal human astrocytes, respectively. The results of the Cell Counting Kit‑8 and Transwell assays revealed that circFLNA knockdown significantly inhibited the proliferative and invasive abilities of GBM cell lines. Moreover, high circFLNA expression levels were associated with a worse prognosis in GBM. MicroRNA (miR)‑199‑3p was subsequently predicted to be target of circFLNA. The inhibitory effect of miR‑199‑3p on cell proliferation and invasion was partially reversed following circFLNA knockdown. In conclusion, the findings of the present study identified novel roles for circFLNA in GBM and indicated that the circFLNA/miR‑199‑3p signaling axis may serve an important role in GBM progression. Therefore, circFLNA may represent a novel target for the diagnosis and treatment of GBM.

Pulmonary arterial hypertension (PAH) is a severe vascular disease that adversely affects patient health and can be life threatening. The present study aimed to investigate the detailed role of nuclear paraspeckle assembly transcript 1 (NEAT1) in PAH. Using RT‑qPCR, the expression levels of NEAT1, microRNA (miR)‑34a‑5p, and Kruppel‑like factor 4 (KLF4) were detected in both hypoxia‑treated pulmonary arterial smooth muscle cells (PASMCs) and serum from PAH patients. Then, the interactions among miR‑34a‑5p, NEAT1, and KLF4 were evaluated by dual‑luciferase reporter assay. The detailed role of the NEAT1/miR‑34a‑5p/KLF4 axis in PAH pathogenesis was further explored using MTT, Transwell, and western blot assays. The results revealed that NEAT1 targeted miR‑34a‑5p and miR‑34a‑5p targeted KLF4. In hypoxia‑treated PASMCs and serum from PAH patients, high NEAT1 and KLF4 expression levels and low miR‑34a‑5p expression were observed. The proliferation and migration of hypoxia‑treated PASMCs were reduced by transfection with sh‑NEAT1 or miR‑34a‑5p mimics. The suppressive effects of NEAT1 knockdown on the proliferation and migration of hypoxia‑treated PASMCs were reversed by knock down of miR‑34a‑5p expression and increased KLF4 expression. NEAT1 was not only highly expressed in the serum of PAH patients but its silencing also alleviated PAH by regulating miR‑34a‑5p/KLF4 in vitro. The present study highlighted a potential new therapeutic target and diagnostic biomarker for PAH.

Mounting evidence has indicated that circular RNAs (circRNAs) serve essential roles in the tumorigenesis and development of various types of cancer. However, the biological functions and the underlying mechanisms of circRNAs in breast cancer (BC) remain largely elusive. In the present study, the expression pattern of circRNAs in three pairs of BC tissues and adjacent normal tissues was determined using a circRNA microarray. The expression and prognostic value of circOMA1 were evaluated by reverse transcription-quantitative PCR in 64 pairs of BC tissues and adjacent normal tissues. Survival curves were generated by the Kaplan-Meier method, and statistical significance was estimated using the log-rank test. A series of in vitro functional experiments were then performed to investigate the role of circOMA1 in the tumorigenesis of BC. The results revealed that the expression levels of circOMA1 were upregulated in BC tissues, and its expression was markedly associated with tumor size and lymph node metastasis. Receiver operating characteristic analysis demonstrated that the expression of circOMA1 could be used to discriminate between BC tissues and adjacent normal tissues. Functionally, overexpression of circOMA1 promoted the viability, migration and invasion of BC cells, whereas circOMA1 knockdown had the opposite effect. Mechanistic investigations showed that circOMA1 promoted the progression of BC by sponging microRNA (miR)-1276 and upregulating sirtuin 4 (SIRT4) expression. In conclusion, circOMA1 may act as an oncogenic circRNA in BC via regulation of the miR-1276/SIRT4 axis.

Vascular smooth muscle cells (VSMCs) serve a decisive role in intimal hyperplasia, a common pathophysiological process that leads to numerous vascular disorders. The present study aimed to investigate the unknown mechanisms underlying VSMC phenotypic modulation and identified a novel microRNA (miRNA/miR)‑17‑5p/homeobox B13 (HOXB13) axis involved in the phenotypic switching, proliferation and migration of VSMCs. VSMCs were isolated from the thoracic aorta of Sprague‑Dawley rats, cell proliferation was determined by Cell Counting Kit‑8 (CCK‑8) assay, cell migration was examined by Transwell migration assay and gene expression was detected using reverse transcription‑quantitative PCR and western blot analyses. It was firstly found that incubation with platelet‑derived growth factor‑BB (PDGF‑BB) recombinant protein resulted in a significant increase in HOXB13 expression in VSMCs. Using multiple miRNA prediction tools, miR‑17‑5p was identified as a potential regulator for HOXB13, since it had a 7‑base perfect binding site and a 5‑base imperfect binding site with the 3'‑untranslated region of HOXB13 mRNA, and these sequences were highly conserved across species. The regulatory effect of miR‑17‑5p on HOXB13 was validated using luciferase reporter assays. The expression level of miR‑17‑5p was increased in VSMCs under PDGF‑BB stimulation, and was negatively correlated with HOXB13 mRNA and protein expression. Moreover, the miR‑17‑5p mimics significantly inhibited the proliferation and migration of VSMCs, while antagomiR‑17‑5p showed the opposite effects, which could be abolished by HOXB13 knockdown. The miR‑17‑5p/HOXB13 axis also regulated the expression levels of the markers of differentiated VSMCs (α‑smooth muscle actin, transgelin and smoothelin), proliferating cell nuclear antigen and cell migration proteins, including MMP‑2 and ‑9. In conclusion, the present study demonstrated that miR‑17‑5p inhibited the phenotypic modulation VSMCs stimulated by PDGF‑BB by downregulating HOXB13, indicating that these factors may be potential therapeutic targets for intimal hyperplasia.