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Background: Endometrial cancer (EC) is an intractable gynecological cancer with increasing incidence and mortality worldwide. Accumulating studies indicated that long noncoding RNA nuclear enriched...

Abstract: Cancer is an important health issue worldwide. Cancer therapy is multifaceted, and drug resistance is still the major limiting factor in the treatment of patients with this disease. Although the mechanisms of anticancer drug resistance have been broadly investigated, a massive biological signal pathway of Non-coding RNAs (ncRNAs) involved in this process has not been completely understood. Long noncoding RNAs (lncRNAs) are a kind of transcripts with a minimum length of 200 nucleotides in size, which have a limited potential for coding proteins. The roles of these RNA molecules have been evaluated in relation to several pathological processes, including tumor formation and progression. Increasing evidence has recently reported that non-coding RNAs (ncRNAs), particularly long non-coding RNAs, have significant roles in many cellular and genomic processes, and because of their potential in regulation specific genes, they are also involved in drug resistance. In this review, we review the literature on the features of lncRNA, their regulation roles in the gene expression related to chemo resistance, and the potential of these RNAs as targeted therapies for personalized treatment in cancers.

Background: Breast cancer is one of the most prevalent cancers that often occur in females. Long noncoding RNA differentiation antagonizing nonprotein coding RNA (DANCR) has been involved in the pathogenesis of various tumors, including breast cancer. This study aimed to investigate the role and underlying mechanism of DANCR in breast cancer. Materials and Methods: The level of DANCR was detected in breast cancer tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell apoptosis was assessed using flow cytometry. Cell migration and invasion were estimated by the Transwell assay. The relationship between DANCR, miR-4319, and vesicle-associated membrane protein-associated protein B (VAPB) was confirmed by bioinformatic analysis and dual-luciferase reporter assay. The level of microRNA-4319 (miR-4319) was tested by qRT-PCR. The expression of VAPB was measured by qRT-PCR or western blot assay. Results: DANCR and VAPB were upregulated, while miR-4319 was downregulated in breast cancer tissues and cells. Knockdown of DANCR hindered proliferation, migration, and invasion and promoted apoptosis of breast cancer cells. DANCR knockdown inhibited breast cancer development through regulating miR-4319. Inhibition of miR-4319 restrained breast cancer cell progression by targeting VAPB. Moreover, DANCR regulated VAPB expression by sponging miR-4319 in breast cancer cells. Conclusion: DANCR facilitated breast cancer cell progression through regulating the miR-4319/VAPB axis, indicating that DANCR might be a potential biomarker and therapeutic target for breast cancer treatment.

Background: This study intended to investigate the mechanisms underlying the epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC). Materials and Methods: Lung cancer tissue samples were collected from 20 patients with NSCLC (6 EGFR mutation types assigned into 2 categories and 14 EGFR wild types assigned to 4 categories). The samples were subjected to transcriptome sequencing, followed by identification of the differentially expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs) between the mutation and nonmutation groups. Function analysis and microRNA (miRNA) prediction for DEMs were performed. The correlations between long noncoding RNA (lncRNA)/circular RNA (circRNA) and messenger RNA (mRNA) were analyzed. In addition, the targeting lncRNA and circRNA of miRNA were predicted. Finally, competing endogenous RNA (ceRNA) network was constructed, and survival analysis for the mRNAs involved in the network was performed. Results: In total, 323 DEMs, 284 DELs, and 224 DECs were identified between EGFR mutation and nonmutation groups. The DEMs were significantly involved in gene ontology functions related to cilium morphogenesis and assembly. ceRNA networks were constructed based on the DEMs, DELs, DECs, and predicted miRNAs. Survival analysis showed that four genes in the ceRNA network, including ABCA3, ATL2, VAMP1, and APLN, were significantly associated with prognosis. The four genes were involved in several ceRNA pathways, including RP1-191J18/circ_000373/miR-520a-5p/ABCA3, RP5-1014D13/let-7i-5p/ATL2, circ_000373/miR-1293/VAMP1, and RP1-191J18/circ_000373/miR-378a-5p/APLN. Conclusion: EGFR mutations in NSCLC may be associated with cilium dysfunction and complex ceRNA regulatory mechanisms. The key RNAs in the ceRNA network may be used as promising biomarkers for predicting EGFR mutations in NSCLC.

Objectives: This study was to investigate the expression and clinical significance of long intergenic noncoding RNA 00665 (LINC00665) in ovarian cancer , as well as its effect on malignant biological behavior of ovarian cancer cells. Methods: The expressions of LINC00665, miR-148b-3p and KLF5 in ovarian cancer (OC) tissues and cells were detected by RT-qPCR. Western blotting was used to detect KLF5 expression. The expression patterns of LINC00665, U6 and GAPDH in nuclear and cytoplasm fractions were detected using qRT-PCR. Besides, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, the interactions between LINC00665 and miR-148b-3p and between miR-148b-3p and KLF5 were verified by luciferase reporter assay, and the correlations among these three genes were analyzed.Results: LINC00665 expression was up-regulated in ovarian cancer cell lines and tissues. Si-LINC00665 inhibited cell proliferation, invasion and migration, and induced the apoptosis to a certain extent. Subcellular fraction assay revealed the location of LINC00665 was mainly situated in the cytoplasm. Besides, miR-148b-3p was a target of LINC00665, and KLF5 was directly targeted by miR-148b-3p. Si-LINC00665 inhibited KLF5 expression, miR-148b-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited LINC00665 expression. Interestingly, expressions of LINC00665 and miR-148b-3p, and expressions of miR-148b-3p and KLF5 were negatively correlated, while expressions of LINC00665 and KLF5 were positively correlated. In addition, si-KLF5 inhibited the malignant biological behavior of ovarian cancer cells, while miR-148b-3p inhibitor had the opposite effect. Most importantly, the si-LINC00665 could reverse the promotion effect of miR-148b-3p inhibitor on the malignant biological behavior of ovarian cancer cells.Conclusions: LINC00665 can be used as an effective prognostic indicator of ovarian cancer, which has the potential to be a new drug target.

Noncoding RNAs (ncRNAs) regulation of various diseases including cancer has been extensively studied. Reactive oxidative species (ROS) elevated by oxidative stress are associated with cancer progression and drug resistance, while autophagy serves as an ROS scavenger in cancer cells. However, the regulatory effects of ncRNAs on autophagy and ROS in various cancer cells remains complex. Here, we explore how currently investigated ncRNAs, mainly miRNAs and lncRNAs, are involved in ROS production through modulating antioxidant genes. The regulatory effects of miRNAs and lncRNAs on autophagy-related (ATG) proteins to control autophagy activity in cancer cells are discussed. Moreover, differential expression of ncRNAs in tumor and normal tissues of cancer patients are further analyzed using The Cancer Genome Atlas (TCGA) database. This review hypothesizes links between ATG genes- or antioxidant genes-modulated ncRNAs and ROS production, which might result in tumorigenesis, malignancy, and cancer recurrence. A better understanding of the regulation of ROS and autophagy by ncRNAs might advance the use of ncRNAs as diagnostic and prognostic markers as well as therapeutic targets in cancer therapy.

Background The abnormal expression of long non-coding RNA (lncRNA) Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) has been observed in many human cancers and the underlying mechanisms have been well studied. However, the function of OIP5-AS1 in acute kidney injury (AKI) remains unclear. Material and methods To explore the role of OIP5-AS1 in the progression of AKI, the cisplatin-induced AKI mouse and cell model were established. To confirm the potential protective effect of OIP5-AS1 during cisplatin-induced AKI, rescue experiments were performed. Targetscan was used to predict the potential targets of miR-144-5p. To further determine whether the effect of miR-144-5p during cisplatin-induced AKI was mediated by PMK2, the recuse experiments using PMK2 overexpressing vector was applied. Results OIP5-AS1 was significantly downregulated both in cisplatin-induced AKI mice and human renal tubular cell line HK-2 cells. Moreover, overexpression of OIP5-AS1 efficiently promoted cell growth and reduced cisplatin-induced apoptosis of HK-2 cells. Furthermore, OIP5-AS1 was identified as a sponge of miR-144-5p, and upregulation of miR-144-5p could significantly reverse overexpression of OIP5-AS1-induced protective effect on the damage of cisplatin to HK-2 cells. In addition, pyruvate kinase M2 (PKM2) was found to be a direct target of miR-144-5p, and overexpression of PKM2 efficiently reversed the effect of miR-144-5p mimics on the damage in cisplatin-stimulated HK-2 cells. Conclusions OIP5-AS1 reduced the apoptosis of cisplatin-stimulated renal epithelial cells by targeting the miR-144-5p/PKM2 axis, which extended the regulatory network of lncRNAs in cisplatin-induced AKI and also provided a novel therapeutic target for AKI treatment.

Understanding of cancer with the help of ever-expanding cutting edge technological tools and bioinformatics is revolutionizing modern cancer research by broadening the space of discovery window of various genomic and epigenomic processes. Genomics data integrated with multi-omics layering have advanced cancer research. Uncovering such layers of genetic mutations/modifications, epigenetic regulation and their role in the complex pathophysiology of cancer progression could lead to novel therapeutic interventions. Although a plethora of literature is available in public domain defining the role of various tumor driver gene mutations, understanding of epigenetic regulation of cancer is still emerging. This review focuses on epigenetic regulation association with the pathogenesis of non-melanoma skin cancer (NMSC). NMSC has higher prevalence in Caucasian populations compared to other races. Due to lack of proper reporting to cancer registries, the incidence rates for NMSC worldwide cannot be accurately estimated. However, this is the most common neoplasm in humans, and millions of new cases per year are reported in the United States alone. In organ transplant recipients, the incidence of NMSC particularly of squamous cell carcinoma (SCC) is very high and these SCCs frequently become metastatic and lethal. Understanding of solar ultraviolet (UV) light-induced damage and impaired DNA repair process leading to DNA mutations and nuclear instability provide an insight into the pathogenesis of metastatic neoplasm. This review discusses the recent advances in the field of epigenetics of NMSCs. Particularly, the role of DNA methylation, histone hyperacetylation and non-coding RNA such as long-chain noncoding (lnc) RNAs, circular RNAs and miRNA in the disease progression are summarized.

Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.

Background: The most prevalent malignant tumor in women is breast cancer (BC). As autophagic therapies have been identified to contribute to BC cell death, the potential prognostic role of long non-coding RNA (lncRNA) related to autophagy in patients with BC was examined. Methods: The lncRNAs expression profiles were derived from The Cancer Genome Atlas (TCGA) database. Throughout univariate Cox regression and multivariate Cox regression test, lncRNA with BC prognosis have been differentially presented. We then defined the optimal cut-off point between high and low-risk groups. The receiver operating characteristic (ROC) curves were drawn to test this signature. In order to examine possible signaling mechanisms linked to these lncRNAs, the Gene Set Enrichment Analysis (GSEA) has been carried out. Results: Based on the lncRNA expression profiles for BC, a 9 lncRNA signature associated with autophagy was developed. The optimal cut-off value for high-risk and low-risk groups was used. The high-risk group had less survival time than the low-risk group. The result of this lncRNA signature was highly sensitive and precise. GSEA study found that the gene sets have been greatly enriched in many cancer pathways. Conclusions: Our signature of 9 lncRNAs related to autophagy has prognostic value for BC, and these lncRNAs related to autophagy may play an important role in BC biology.

Introduction Sepsis is an infection-induced severe inflammatory disorder leading to multiple organ dysfunction. It remains a highly lethal condition for which early diagnosis and therapy achieve unsatisfactory results. Circulating exosomes containing biomarkers and mediators of sepsis have recently received attention, but the progress has been far from optimal. Objectives The present study focuses on the profiles of molecular dynamics in serum exosomes and explores the potential molecular mechanisms on serum exosomes during the process of sepsis. Methods We used high-performance liquid chromatography-tandem mass spectrometry and RNA-seq to detect the dynamic profiles of exosome proteins and RNAs (including mRNAs, lncRNAs and miRNAs) in serum exosomes from 3 healthy individuals and 9 septic patients at the different stages. Then integrative multiomics analyses were performed and the results were validated by qRT-PCR, LiquiChip assay and metabolomics analysis on mice subjected to cecal ligation and puncture (CLP) modeling. Results A total of 354 proteins, 195 mRNAs, 82 lncRNAs and 55 miRNAs were identified as differentially expressed molecules in serum exosomes from septic patients. Integrative multiomics analysis showed that exosome components were associated with cytokine storm, complement and clotting cascades, the endothelial barrier, 20S proteasome-dependent protein degradation and vitamin metabolism. Importantly, pretreatment with serum exosomes derived from mice subjected to CLP significantly restrained proinflammatory cytokine expression and alleviated tissue injury in septic mice. Further metabolomics analysis demonstrated that pretreatment with septic serum exosomes significantly affected the metabolites associated with vitamin digestion and absorption in CLP mice. Conclusion Our study for the first time describes the landscape of the molecular dynamics of serum exosomes during the development of sepsis and proposes some hypothetical molecular mechanisms by integrative multiomics analysis, which may provide helpful diagnostic and therapeutic insights for the ongoing battle against sepsis.

Gastrointestinal (GI) cancers presented an alarmingly high number of new cancer cases worldwide and are highly characterised by poor prognosis. The poor overall survival is mainly due to late detection and emerging challenges in treatment, particularly chemoresistance. Thus, the identification of novel molecular targets in GI cancer is highly regarded as the main focus. Recently, long non-coding RNAs (lncRNAs) have been discovered as potential novel molecular targets for combating cancer, as they are highly associated with carcinogenesis and have a great impact on cancer progression. Amongst lncRNAs, HOTTIP has demonstrated a prominent oncogenic regulation in cancer progression, particularly in GI cancers, including oesophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. This review aimed to present a focused update on the regulatory roles of HOTTIP in GI cancer progression and chemoresistance, as well as deciphering the associated molecular mechanisms underlying their impact on cancer phenotypes and chemoresistance and the key molecules involved. It has been reported that it regulates the expression of various genes and proteins in GI cancers that impact cellular functions, including proliferation, adhesion, migration and invasion, apoptosis, chemosensitivity, and tumour differentiation. Furthermore, HOTTIP was also discovered to have a higher diagnostic value as compared to existing diagnostic biomarkers. Overall, HOTTIP has presented itself as a novel therapeutic target and potential diagnostic biomarker in the development of GI cancer treatment.

As a novel group of non-coding RNAs, long non-coding RNA (lncRNAs) can substantially regulate various biological processes. Downregulated tumor-suppressive lncRNAs and upregulated oncogenic lncRNAs (onco-lncRNAs) have been implicated in gastric cancer (GC) development. These dysregulations have been associated with decreased chemosensitivity, inhibited apoptosis, and increased tumor migration in GC. Besides, growing evidence indicates that lncRNAs can be a valuable diagnostic and prognostic biomarker, and their expression levels are substantially associated with the clinicopathological features of affected patients. The current study aims to review the recent findings of the tumor-suppressive lncRNAs and onco-lncRNAs in GC development and highlight their therapeutic, diagnostic, and prognostic values in treating GC cells. Besides, it intends to highlight the future direction of lncRNAs in treating GC.

Acute lung injury (ALI) induced by bacteria lipopolysaccharide (LPS) is characterized by the upregulation of the apoptosis rate of tissue cells and aggravation of inflammatory response. Although many studies have focused on the pathogenesis of this disease, its mechanism remains unknown. This study examined the regulatory role of long non-coding RNA (lncRNA) LINC01194 in the progression of ALI through various bioinformatics analyses and experimental work, including ELISA assay, dual-luciferase reporter assay, biotinylated RNA pull-down assay, and Western blot analysis. The result showed that the LINC01194 was overexpressed in the ALI-induced mice model. We observed a significant upregulation of LINC01194 in LPS-treated mouse lung epithelial type II cells (MLE-12 cells) after 24 h of induction. Bioinformatics analysis, ELISA assay, quantitative reverse transcription polymerase chain reaction analysis, biotinylated RNA pull-down assay, apoptosis test, and Western blot analysis demonstrated that the LINC01194 could act as a microRNA (miR) miR-203a-3p sponge to activate the inflammatory response in LPS-induced ALI model through post-transcriptional upregulation of macrophage inflammatory protein (MIP-2). We showed that LINC01194 regulates the inflammatory response and apoptosis of LPS-induced mice and MLE-12 cells via the miR-203a-3p/MIP-2 axis. LINC01194 could be a potential biomarker for early diagnosis and the treatment of ALI.

Abstract: Aging refers to a natural process and a universal phenomenon in all cells, tissues, organs, and the whole organism. Long non-coding RNAs (lncRNAs) are non-coding RNAs with a length of 200 nucleotides. LncRNA growth arrest-specific 5 (lncRNA GAS5) is often down-regulated in cancer. The accumulation of lncRNA GAS5 has been found to be able to inhibit cancer growth, invasion, and metastasis while enhancing the sensitivity of cells to chemotherapy drugs. LncRNA GAS5 can be a signaling protein, which is specifically transcribed under different triggering conditions. Subsequently, it is involved in signal transmission in numerous pathways as a signal node. LncRNA GAS5, with a close relationship to multiple miRNAs, was suggested to be involved in the signaling pathway under three action modes (i.e., signal, bait, and guidance). LncRNA GAS5 was found to be involved in different age-related diseases (e.g., rheumatoid arthritis, type 2 diabetes, atherosclerosis, osteoarthritis, osteoporosis, multiple sclerosis, cancer, etc.). This study mainly summarized the regulatory effect exerted by lncRNA GAS5 on age-related diseases.

Background: Smoking participates in pathogenesis of lung cancer. Long non-coding RNAs (lncRNAs) play some specific roles during development of lung cancers. Objective: To investigate effects of smoking on lncRNA alterations in lung cancer. Methods: There are 522 lung adenocarcinoma (LUAD) and 504 lung squamous cell carcinoma (LUSC) participants. Clinical and lncRNA genetic data were downloaded from The Cancer Genome Atlas (TCGA) database. LncRNA alterations were analyzed in lung cancer patients. Smoking category and packs were evaluated. Correlations between smoking and LncRNA alterations were analyzed. Kaplan-Meier analysis was performed to determine overall survival and disease free survival. Results: There are more non-smokers in LUSC than in LUAD. In both LUAD and LUSC, smoking could increase total mutation counts and fraction of copy number alterations. Smoking index positively correlated with total mutations in LUAD, but not in LUSC. Smoking could trigger lncRNA alterations both in LUAD and LUSC. Smoking regulated different lncRNA between male and female. EXOC3-AS1 and LINC00603 alterations were positively correlated with smoking index in male LUAD smokers. In female LUAD smokers, smoking index was positively correlated with SNHG15, TP53TG1 and LINC01600 and negatively with LINC00609 and PTCSC3. In both male and female LUSC patients, smoking increased or decreased several lncRNA alterations. DGCR5 alteration increased in male LUSC than in female LUSC patients. In female LUSC patients, LOH12CR2 alteration was positively correlated with smoking index. Conclusions: Smoking promoted LUAD and LUSC development by affecting different lncRNA alterations in different genders.

Research question Whether extracellular vesicle-derived lncRNAs could serve as promising circulating biomarkers for endometriosis? Design To obtain novel diagnostic markers, we enrolled 85 patients with endometriosis as the endometriosis group and 86 unaffected participants as the control group. RNA sequencing was performed to identify exosomal long non-coding RNAs (lncRNAs) that are differentially expressed between women with endometriosis (n=5) and unaffected participants (n=6). Messenger RNA and lncRNA sequences of the plasma exosomes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. LncRNA expression levels were further validated using quantitative reverse transcriptase polymerase chain reaction. Moreover, receiver operating characteristic curve analysis was performed to determine the diagnostic value of candidate lncRNAs. Clinical features were correlated to the expression levels of candidate lncRNAs. Results We found that 210 lncRNAs were significantly dysregulated; among these, expression of LINC01569, RP3-399L15.2, FAM138B, and CH507-513H4.6 was significantly decreased, whereas expression of RP11-326N17.2, KLHL7-AS1, and MIR548XHG was increased, in the plasma of patients with endometriosis. Combined expression level of RP3-399L15.2 and CH507-513H4.6 was used to distinguish patients with endometriosis from control participants; the results revealed a sensitivity of 80.00% and specificity of 85.45% at the cutoff point, and an area under the ROC curve of 0.9045. Our findings demonstrated the potential of these two lncRNAs as diagnostic biomarkers for endometriosis. Moreover, CH507-513H4.6 alone may be useful to detect early-stage endometriosis lesions. Conclusions The combination of RP3-399L15.2 and CH507-513H4.6 can be potential candidates for endometriosis biomarkers.

Gastric cancer is a global cancer with a high mortality rate. A growing number of studies have found the abnormal expression of lncRNA (long noncoding RNA) in many tumors, which plays a role in promoting or inhibiting cancer. Similarly, lncRNA abnormal expression plays an essential biological function in gastric cancer. This article focuses on lncRNA involvement in the development of gastric cancer in terms of cell cycle disorder, apoptosis inhibition, metabolic remodeling, promotion of tumor inflammation, immune escape, induction of angiogenesis, and Epithelial Mesenchymal Transition (EMT). The involvement of lncRNA in the development of gastric cancer is related to drug resistance, such as cisplatin and multi-drug resistance. It can also be used as a potential marker for the diagnosis and prognosis of gastric cancer and a target for the treatment. With an in-depth understanding of the mechanism of lncRNA in gastric cancer, new ideas for personalized treatment of gastric cancer are expected.

BACKGROUND: Colorectal cancer (CRC), one of the most common human malignancies, is a leading cause of the cancer-related mortality. 5-FU is a first-line chemotherapeutic agent against CRC. Although CRC patients responded to 5-FU therapy initially, a part of patients succumbed to CRC due to the acquired drug resistance. Thus, investigating molecular mechanisms underlying chemoresistance will contribute to developing novel strategies against colorectal cancer. OBJECTIVE: Accumulation evidence revealed pivotal roles of long non-coding RNAs (lncRNAs) in tumorigenesis and chemoresistance of CRC. However, the precise roles and molecular mechanisms of lncRNA-HCG11 in CRC remain unclear. This study aimed to investigate the biological roles and underlying mechanisms of HCG11 as well as its molecular targets in regulating the cellular metabolism processes, which facilitate the chemoresistance of CRC. METHODS AND RESULTS: This study uncovers that HCG11 was significantly upregulated in CRC tumors tissues and cell lines. Moreover, HCG11 was elevated in 5-FU resistant CRC tumors. Silencing HCG11 inhibited colon cancer cell proliferation, migration, invasion and glucose metabolism and sensitized CRC cells to 5-FU. In addition, we detected increased HCG11 expression level and glucose metabolism in the established 5-FU resistant CRC cell line (DLD-1 5-FU Res). Furthermore, microRNA-microArray, RNA pull-down and luciferase assays demonstrated that HCG11 inhibited miR-144-3p which displays suppressive roles in colon cancer via sponging it to form a ceRNA network. We identified pyruvate dehydrogenase kinase 4 (PDK4), which is a glucose metabolism key enzyme, was directly targeted by miR-144-3p in CRC cells. Rescue studies validated that the miR-144-3p-inhibited glucose metabolism and 5-FU sensitization were through targeting PDK4. Finally, restoration of miR-144-3p in HCG11-overexpressing DLD-1 5-FU resistant cells successfully overcame the HCG11-faciliated 5-FU resistance via targeting PDK4. CONCLUSION: In summary, this study reveals critical roles and molecular mechanisms of the HCG11-mediated 5-FU resistance through modulating the miR-144-3p-PDK4-glucose metabolism pathway in CRC.

BACKGROUND: The disorder of LINC01207 has a significant regulatory effect on cancers, nevertheless its role in non-small cell lung cancer (NSCLC) have not been illustrated. This study investigated the regulatory effect of LINC01207 on NSCLC and clarify its molecular mechanism. METHODS: Bioinformatics analysis was used to find the target lncRNA, miRNA and mRNA. LncBase and TargetScan databases predicted the relationship between LINC01207, miR-525-5p and ARHGAP11A. Dual-luciferase reporter gene assay and RNA binding protein immunoprecipitation assay were used to verify the binding relationship between genes. Fluorescence in situ hybridization assay was used to localize the expression of LINC01207 in NSCLC tissue. qRT-PCR and Western blot assays were used to measure the expression of LINC01207, miR-525-5p and ARHGAP11A. CCK-8 assay, Transwell assay and flow cytometry assay were used to detect NSCLC cell abilities. Mouse xenograft models further determined the effect of LINC01207 on the growth of NSCLC in vivo. RESULTS: LINC01207 was up-regulated in NSCLC tissue and cells, which was mainly localized in the cytoplasm. LINC01207 knockdown could inhibit the proliferation, migration and invasion of cancer cells and induce cell apoptosis. In addition, silencing LINC01207 could suppress tumor growth in vivo. LINC01207 could sponge and inhibit the expression of miR-525-5p in NSCLC cells, and inhibiting LINC01207 and miR-525-5p simultaneously could reverse the effect of miR-525-5p on the progression of NSCLC cells. Further study on downstream target genes showed that miR-525-5p could restrain the expression of ARHGAP11A, and then affect the progression of NSCLC. LINC01207 acting as a competing endogenous RNA (ceRNA) could regulate the expression of ARHGAP11A by competitively binding with miR-525-5p. CONCLUSION: LINC01207 regulates the progression of NSCLC by regulating the miR-525-5p/ARHGAP11A axis as a ceRNA and plays a carcinogenic role. In conclusion, our study elucidates the mechanism of LINC01207 regulating the progression of NSCLC, and provides a new idea for the diagnosis and treatment of NSCLC guided by lncRNA.

Periodontal disease is an inflammatory reaction of the periodontal tissues to oral pathogens. In the present review we discuss the intricate effects of a regulatory network of gene expression modulators, microRNAs (miRNAs), as they affect periodontal morphology, function and gene expression during periodontal disease. These miRNAs are small RNAs involved in RNA silencing and post-transcriptional regulation and affect all stages of periodontal disease, from the earliest signs of gingivitis to the regulation of periodontal homeostasis and immunity and to the involvement in periodontal tissue destruction. MiRNAs coordinate periodontal disease progression not only directly but also through long non-coding RNAs (lncRNAs), which have been demonstrated to act as endogenous sponges or decoys that regulate the expression and function of miRNAs, and which in turn suppress the targeting of mRNAs involved in the inflammatory response, cell proliferation, migration and differentiation. While the integrity of miRNA function is essential for periodontal health and immunity, miRNA sequence variations (genetic polymorphisms) contribute toward an enhanced risk for periodontal disease progression and severity. Several polymorphisms in miRNA genes have been linked to an increased risk of periodontitis, and among those, miR-146a, miR-196, and miR-499 polymorphisms have been identified as risk factors for periodontal disease. The role of miRNAs in periodontal disease progression is not limited to the host tissues but also extends to the viruses that reside in periodontal lesions, such as herpesviruses (human herpesvirus, HHV). In advanced periodontal lesions, HHV infections result in the release of cytokines from periodontal tissues and impair antibacterial immune mechanisms that promote bacterial overgrowth. In turn, controlling the exacerbation of periodontal disease by minimizing the effect of periodontal HHV in periodontal lesions may provide novel avenues for therapeutic intervention. In summary, this review highlights multiple levels of miRNA-mediated control of periodontal disease progression, (i) through their role in periodontal inflammation and the dysregulation of homeostasis, (ii) as a regulatory target of lncRNAs, (iii) by contributing toward periodontal disease susceptibility through miRNA polymorphism, and (iv) as periodontal microflora modulators via viral miRNAs.

Colorectal cancer (CRC) is the third main cause of cancer-relevant deaths worldwide, and its incidence has increased in recent decades. Previous studies have indicated that certain long noncoding RNAs (lncRNAs) have regulatory roles in tumor occurrence and progression. Often, lncRNAs are competitive endogenous RNAs that sponge microRNAs to up-regulate mRNAs. Here, we examined the role of a novel lncRNA gamma-butyrobetaine hydroxylase 1 antisense RNA 1 (BBOX1-AS1) in CRC. We observed that BBOX1-AS1 is overexpressed in CRC cell lines, and BBOX1-AS1 knockdown enhances cell proliferation, migration and invasion while reducing cell apoptosis. miR-361-3p is present at a low level in CRC and is negatively modified by BBOX1-AS1. Moreover, miR-361-3p was validated to be targeted by BBOX1-AS1. Src homology 2 B adaptor protein 1 (SH2B1) was notably upregulated in CRC cell lines and was identified as a downstream gene of miR-361-3p. In addition, we found that miR-361-3p amplification can suppress the expression of SH2B1. Finally, data from rescue assays suggested that overexpression of SH2B1 counteracted BBOX1-AS1 silencing-mediated inhibition of CRC progression. In conclusion, BBOX1-AS1 promotes CRC progression by sponging hsa-miR-361-3p and up-regulating SH2B1.

Background/Aim: Long noncoding RNA TARID (lncRNA TARID) can activate the tumor suppressor TCF21 in tumorigenesis by inducing promoter demethylation. However, the impact on lncRNA TARID and its variants of coronary artery disease (CAD) are poorly understood. Methods We performed a case-control study enrolling 949 case patients and 892 controls to assess genotype. Five variants were genotyped by TaqMan assay. 20 case patients and 20 controls were used to evaluate the expression of lncRNA TARID. The qRT-PCR and cell cycle analysis were applied to examined cell proliferation and cell distribution. Results This study indicated that rs2327433 GG genotype was associated with CAD risk adjusting for traditional risk factors (OR=2.74, 95%CI: 1.10-6.83, P=0.03). Our results analyses revealed that the genotype of rs2327433 was related to the proportion of CAD patients with left anterior descending artery disease and left circumflex artery disease (P=0.025 and P=0.025, respectively). The results showed that the minor allele frequency of rs2327433 was significantly correlated with the severity of the disease (P=0.029). The eQTL analysis showed that rs2327433 may affect the transcription factors TCF21 regulated by lncRNA TARID. We found that TARID silencing regulated the cell proliferation and altered cell cycle progression by induced upregulation of CDK1 and PCNA. Conclusions SNP rs2327433 in lncRNA TARID was associated with CAD risk and the severity of CAD in Chinese Han population. Furthermore, SNP rs2327433 may affect the expression of atherosclerosis-related transcription factor TCF21 regulated by lncRNA TARID. Finally, our study provided a new lncRNA-dictated regulatory mechanism participating in cell proliferation.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. The aim of our study was to investigate the potential mechanism in DN progression. SV40 mesangial cells (MES)13 cells were exposed to high concentration of glucose (HG: 30 mmol/L) for 48 hours to establish a DN cell model in vitro. Bioinformatic software StarBase was adopted to establish the long noncoding RNA (lncRNA)-microRNA-messenger RNA axis. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay were performed to verify intermolecular interaction. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was overexpressed in the serum of patients with DN. HG time-dependently upregulated NEAT1 levels, and HG promotes cell proliferation, oxidative stress, inflammation, and fibrosis and suppressed cell apoptosis in SV40 MES13 cells partly through upregulating NEAT1. NEAT1 functioned as a molecular sponge of miR-423-5p, and NEAT1 silencing-mediated effects were partly overturned by miR-423-5p interference in HG-induced SV40 MES13 cells. Glioma pathogenesis related-2 (GLIPR2) was a target of miR-423-5p. GLIPR2 overexpression in normal concentration of glucose (NG)-induced SV40 MES13 cells partly simulated HG-induced effects. GLIPR2 overexpression partly reversed NEAT1 interference-induced effects in HG-induced SV40 MES13 cells. LncRNA NEAT1 contributed to HG-induced DN progression through the miR-423-5p/GLIPR2 axis in vitro. NEAT1/miR-423-5p/GLIPR2 axis might be a potential target for DN treatment.

Introduction Tumors are usually refractory to anti-cancer therapeutics under hypoxic conditions. However, the underlying molecular mechanism remains to be elucidated. Objectives Our study intended to identify hypoxia inducible lncRNAs and their biological function in gastric cancer (GC). Methods Differentially expressed lncRNAs were determined by microarray analysis between GC cells exposed to hypoxia (1% O2) and normoxia (21% O2) for 24 h. The expression level of CBSLR was manipulated in several GC cell lines to perform molecular and biological analyses both in vitro and in vivo. Results We identified a hypoxia-induced lncRNA-CBSLR that protected GC cells from ferroptosis, leading to chem-resistance. Mechanically, CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Furthermore, under decreased CBS levels, the methylation of the ACSL4 protein was reduced, leading to protein polyubiquitination and degradation of ACSL4. This, in turn, decreased the pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) and PE (18:0/22:4) content and contributed to ferroptosis resistance. Notably, CBSLR is upregulated, whereas CBS is downregulated in GC tissues compared to matched normal tissues; and GC patients with high CBSLR/low CBS levels have a worse clinical outcome and a poorer response to chemotherapy. Conclusion Our study reveals a novel mechanism in how HIF1α/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.

Heart failure is mainly caused by a decline in the systolic function of the heart. Long noncoding RNAs are related to cardiac diseases. This study aimed to explore the effects of long noncoding RNAs testis development related gene 1 (TDRG1) on the fibrogenesis and inflammatory response of transforming growth factor-beta1 (TGF-β1)-stimulated human cardiac fibroblasts (HCFs). Levels of proinflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Reverse-transcription quantitative polymerase chain reaction was applied to reveal the expression levels of TDRG1, miR-605-3p, and tumor necrosis factor receptor superfamily (TNFRSF21). Western blot analysis was prepared to detect protein levels of TNFRSF21 and fibrosis-related genes. Luciferase reporter assay was conducted for confirming the interaction between miR-605-3p and TDRG1/TNFRSF21. We found that TGF-β1-stimulated HCFs showed high concentrations of proinflammatory cytokines and increased protein levels of fibrosis-related genes, suggesting the dysfunctions of TGF-β1-stimulated HCFs. In addition, TDRG1 was upregulated in TGF-β1-stimulated HCFs. We found that interfering with TDRG1 alleviated dysfunctions of TGF-β1-stimulated HCFs. Moreover, TDRG1 bound with miR-605-3p. MiR-605-3p exerted the antifibrogenic and anti-inflammatory effects in TGF-β1-treated HCFs. As a target gene of miR-605-3p, TNFRSF21 reversed the antifibrogenic and anti-inflammatory effects of TDRG1 knockdown in TGF-β1-treated HCFs. Overall, our study confirmed that TDRG1 aggravates fibrogenesis and inflammatory response in TGF-β1-treated HCFs via the miR-605-3p/TNFRSF21 axis.

Cardiovascular diseases (CVDs) are major causes of morbidity and mortality worldwide. Great effort has been put into exploring early diagnostic biomarkers and innovative therapeutic strategies for preventing CVD progression over the last two decades. Long non-coding RNAs (lncRNAs) have been identified as novel regulators in cardiac development and cardiac pathogenesis. For example, lncRNA H19 (H19), also known as a fetal gene abundant in adult heart and skeletal muscles and evolutionarily conserved in humans and mice, has a regulatory role in aortic aneurysm, myocardial hypertrophy, extracellular matrix reconstitution, and coronary artery diseases. Yet, the exact function of H19 in the heart remains unknown. This review summarises the functions of H19 in the heart and discusses the challenges and possible strategies of H19 research for cardiovascular disease.

LncRNA ELF3-AS1 has been characterized as an oncogenic lncRNA in bladder cancer and oral cancer, whereas its role in non-small cell lung cancer (NSCLC) is unknown. In this study, the authors observed that ELF3-AS1 was upregulated in NSCLC tissues in comparison with that in paired nontumor tissues collected from 68 NSCLC patients. High expression levels of ELF3-AS1 predicted the poor survival of NSCLC patients. Expression levels of miR-212 were inversely and significantly correlated with the expression levels of ELF3-AS1 across NSCLC tissue samples. In NSCLC cells, overexpression of ELF3-AS1 led to downregulated miR-212 and increased methylation of miR-212 gene. In addition, overexpression of ELF3-AS1 inhibited the role of miR-212 in suppressing cancer cell invasion and migration. Therefore, ELF3-AS1 is upregulated in NSCLC and promotes cancer cell invasion and migration by downregulating miR-212 through methylation.

Background Dysregulation of BZRAP1‐AS1 was associated with immune statuses of cancer or Alzheimer's disease patients, yet little is known about its role in rheumatoid arthritis. Methods RT‐qPCR and western blot were applied to assess the expression of indicated expression. CCK‐8 and BrdU proliferation assays were used to measure the proliferation of RA‐HFLS. Apoptosis in RA‐HFLS was evidenced by the alteration of caspase‐3 activity and apoptosis‐related factors. ELISA was performed to detect IL‐6, IL‐1β, and TNF‐α level. Luciferase reporter, RIP, and pull‐down assays were used to confirm the BZRAP1‐AS1/miR‐1286/COL5A2 cascade predicted by bioinformatics analysis. Results BZRAP1‐AS1 and COL5A2 were downregulated in RA tissues and RA‐HFLS while miR‐1286 was amplified. Overexpression of BZRAP1‐AS1 reduced the RA‐HFLS proliferation, IL‐6, IL‐1β, and TNF‐α level and induced cell apoptosis while BZRAP1‐AS1 silence produced an opposite effect. Overexpression of BZRAP1‐AS1 reduced the miR‐1286 expression which in turn increased the COL5A2 expression, thereby relieving the excessive proliferation and limited apoptosis in RA‐HFLS. Conclusion Our findings suggested that BZRAP1‐AS1 sequestered miR‐1286 and reshaped the COL5A2 expression, thereby suppressed RA‐HFLS proliferation and inflammation, and triggered cell apoptosis, resulting in the attenuation of RA progression.

Moyamoya disease (MMD) is an idiopathic cerebrovascular disease with unknown etiology. Long noncoding RNA (lncRNA) and messenger RNA (mRNA) profiles in MMD remain unknown. In this current study, we aim to investigate lncRNA-mRNA co-expression pattern and their biological functions in superficial temporal artery (STA) of MMD.STA of 3 MMD patients without RNF213 mutation and 3 age-matched controls were obtained for transcriptomic RNA sequencing. Bioinformatics analysis was performed to investigate their molecular functions and interactions. Then, differentially expressed genes relative to vascular remodeling were further validated by quantitative real-time polymerase chain reaction and immunofluorescence. WNT5A functions were tested by tube formation assay and wound scratching assay in human microvascular endothelial cells (HMECs).We detected 6235 different lncRNAs and 2065 different mRNAs from the RNA-sequencing between MMD patients and controls (P0.05; fold change2.0). Gene ontology showed that altered mRNAs were enriched for endothelial cell morphogenesis and positive regulation of angiogenesis, which were closely related with vascular remodeling. We then searched 76 altered genes related with vascular remodeling and applied Kyoto Encyclopedia of Genes and Genomes analysis. Integrated analysis of lncRNA-TF-mRNA co-expression networks and gene verifications indicated that molecular including WNT5A, TEK, and GATA2 may contribute to the vascular malformation of MMD. Overexpression of WNT5A in HMECs promoted tube formation and cell migration.In MMD patients, genes related to vascular remodeling including WNT5A and their regulators were aberrantly disrupted. These results will help elucidate the complicated pathogenic mechanism of MMD and develop potential therapeutic targets facilitating MMD angiogenesis in the future.

Cancer‐associated fibroblasts (CAF) are the most abundant stromal cells in tumor and exert a pro‐tumoral effect in cancer progression. Numerous evidence shows long non‐coding RNA (lncRNA) abnormally regulates gene expression in various cancers. However, little is known about the role of lncRNA in the interaction between CAF and cancer cells. Here, we first identify an uncharacterized lncRNA, LOC100506114, which is significantly upregulated in CAF and is involved in the functional transformation of normal fibroblasts (NF) and CAF. Expression of LOC100506114 enhances the expression of fibroblast activation protein alpha and α‐smooth muscle actin in NF and promotes malignant characteristics of NF and CAF in vivo and in vitro. The profile of gene co‐expression analysis shows that growth differentiation factor 10 (GDF10) is positively correlated with the expression of LOC100506114. CAF promote stromal fibroblast activation and the proliferation and migration of tumor cells by secreting GDF10. Our data demonstrate that lncRNA plays a critical role in the interplay of stromal fibroblasts and tumor cells in oral squamous cell carcinoma., Abnormal expression of lncRNA LOC100506114 in oral squamous cell carcinoma (OSCC) induced normal fibroblasts (NF) to transform into CAF by upregulating growth differentiation factor 10 (GDF10) expression and secretion. The interaction of GDF10 with the transcription factor RUNX family transcription factor 2 further enhanced the growth and migration of OSCC tumor cells by activating the TGFβRI/Smad3/ERK pathway. Our results demonstrate that lncRNA play an important role in the functional transformation of human NF into CAF and promote OSCC tumorigenesis.

Long noncoding RNAs (lncRNAs) have a profound effect on biological processes in various malignancies. However, few studies have investigated their functions and specific mechanisms in endometrial cancer. In this study, we focused on the role and mechanism of lncRNA‐ZXF1 in endometrial cancer. Bioinformatics and in vitro and in vivo experiments were used to explore the expression and function of lncRNA‐ZXF1. We found that lncRNA‐ZXF1 altered the migration and invasion of endometrioid endometrial cancer (EEC) cells. Furthermore, our results suggest that lncRNA‐ZXF1 regulates EEC cell proliferation. This regulation may be achieved by the lncRNA‐ZXF1‐mediated alteration in the expression of P21 through two mechanisms. One is that lncRNA‐ZXF1 functions as a molecular sponge of miR‐378a‐3p to regulate PCDHA3 expression and then modulate the expression of P21. The other is that lncRNA‐ZXF1 inhibits CDC20‐mediated degradation of ubiquitination by directly binding to P21. To the best of our knowledge, this study is the first to explore lncRNA‐ZXF1 functioning as a tumor‐suppressing lncRNA in EEC. LncRNA‐ZXF1 may become therapeutic, diagnostic, and prognostic indicator in the future., In this study, we found that lncRNA‐ZXF1 may act as a tumor suppressor gene to regulate the proliferation and invasion of endometrioid endometrial cancer (EEC). LncRNA‐ZXF1 potentially alters P21 expression in EEC through two mechanisms: by regulating P21 protein expression through the miR‐378a‐3p/PCDHA3 axis and by directly binding to P21 to prevent its CDC20‐mediated ubiquitin degradation.

The relationship between microRNA (miRNA) and hosting long non-coding RNA (lncRNA) remains unclear. Here, the expression levels of microRNA-210 (miR-210) and hosting lncRNA MIR210HG are significantly increased and positively correlated in gastric cancer (GC). Gain- and loss-of-function studies demonstrate that miR-210 and MIR210HG synergistically promote the migration and invasion of GC cells in vitro. Furthermore, GC sublines simultaneously expressing miR-210 and MIR210HG display synergistic promotion of lung metastasis in vivo. Mechanistically, MIR210HG interacts with DExH-box helicase 9 (DHX9) to increase DHX9/c-Jun complex's occupancy on the promoter of matrix metallopeptidases (MMPs), and thus promotes migration and invasion of GC cells. Additionally, miR-210 directly suppresses the expression of dopamine receptor D5 (DRD5), serine/threonine kinase 24 (STK24) and MAX network transcriptional repressor (MNT), resulting in enhanced migration and invasion. Finally, MYC proto-oncogene (c-Myc) transactivates miR-210 and MIR210HG. Overexpression of miR-210 or/and MIR210HG can rescue the inhibitory effect on the migration and invasion by silencing c-Myc. Moreover, c-Myc inhibitor significantly decreases lung metastasis of GC in vivo. Collectively, our findings identify a novel mechanism, by which c-Myc-activated miR-210 and MIR210HG synergistically promote the metastasis of GC.

Estrogen receptor alpha (ERα) plays a vital role in the development of normal breast tissue and in breast cancer. By cross-analyzing The Cancer Genome Atlas (TCGA) database, ERα-regulated long noncoding RNA 1 (ERLC1) was identified as a long noncoding RNA exhibiting a strong association with ERα signaling and high specificity of expression in breast tissue. ERLC1 was transcriptionally activated by ERα, and ERLC1 stabilized the ESR1 transcript by sequestering miR-129 and tethering FXR1 to maintain a positive feedback loop that potentiated ERα signaling. ERLC1 was elevated in tamoxifen-resistant breast cancer cells, where ERLC1 depletion restored sensitivity to tamoxifen and increased the efficacy of palbociclib or fulvestrant therapy. Collectively, these data warrant further investigation of ERLC1 as a modulator of therapeutic response and potential therapeutic target in ER+ breast cancer. Significance: This study identifies an estrogen-regulated lncRNA and the mechanism by which it positively regulates ERα activity, demonstrating a feedback loop that can promote resistance to antiestrogen therapies in ER+ breast cancer.

Background Hepatocellular carcinoma (HCC) is usually diagnosed at late stages, making it the second cause of malignancy-related death across the world. Long noncoding RNAs (lncRNAs) are of significance to tumorigenesis, highly suggestive of their functional roles as novel biomarkers for cancer therapy. The current study investigated the specific role of lncRNA TPTE pseudogene 1 (TPTEP1) in HCC. Methods Expression of lncRNA TPTEP1, microRNA-454-3p (miR-454-3p) and discs large homolog 5 (DLG5) was determined in tissues samples from the recruited patients with HCC. Cell proliferation, migration and invasion assays were performed to determine effects of lncRNA TPTEP1, miR-454-3p and DLG5 on the malignant phenotype of tumor cells. Finally, the mouse HCC model was also established to disclose the tumor suppressor effects of lncRNA TPTEP1 in vivo. Results LncRNA TPTEP1 was downregulated both in HCC cells and tissues, and played a negative regulatory role in HCC cell proliferation, migration and invasion. Mechanistically, lncRNA TPTEP1 competitively bound to miR-454-3p, thereby upregulating its endogenous target DLG5. Moreover, lncRNA TPTEP1 hindered activation of the protein kinase B signaling pathway, causing inhibited malignant phenotypes of HCC cells. Also, lncRNA TPTEP1 suppressed tumor growth and extrahepatic metastasis (lung) via miR-454-3p/DLG5 axis. Conclusion Taken together, this research revealed a concrete mechanism of lncRNA TPTEP1 in HCC.

Background Breast cancer is the most common malignant tumor in women and is not easy to diagnose. Increasing evidence has underscored that long non-coding RNAs (lncRNAs) play important regulatory roles in the occurrence and progression of many cancers, including breast cancer. We aimed to identify lncRNAs in plasma as potential biomarkers for breast cancer. Patients and Methods We analyzed the Gene Expression Omnibus (GEO) datasets GSE22820, GSE42568, and GSE65194 to identify the common differential genes between cancer tissues and adjacent tissues. Then 14 lncRNAs were identified among the common differential genes and validated by using real-time quantitative polymerase chain reaction in 92 patients with breast cancer and 100 healthy controls. Receiver operating characteristic (ROC) curves were constructed to evaluate their diagnostic value for breast cancer. Results Integrated analysis of the GEO datasets identified three significantly upregulated and 11 downregulated lncRNAs in breast cancer tissues. Compared with healthy controls, MIAT was significantly upregulated in breast cancer patient plasma, and LINC00968 and LINC01140 were significantly downregulated. ROC curve analysis suggested that these three lncRNAs can discriminate breast cancer from healthy individual with high specificity and sensitivity. Conclusion This research identified three differentially expressed lncRNAs in breast cancer patient plasma. Our data suggest that these three lncRNAs can be used as potential diagnostic biomarkers of breast cancer.

Atherosclerotic lesions of the coronary arteries are still in charge of significant annual morbidity and mortality despite intense therapeutic advancements. Genome-born elements contribute substantially to the atherosclerosis process. ANRIL is one of the long non-coding RNAs with outstanding functions particularly regulation of genes involved in atherosclerosis development. In this study, we measured ANRIL expression (circular-, linear-, and circular/linear ratio) in hypertensive patients with coronary artery disease (CAD) compared with peers without CAD. Among hypertensive patients who were candidates of angiography, 25 subjects with CAD and the equal number without CAD were considered as the case and control groups, respectively. Different categories of data were recorded through a predefined questionnaire. Before angiography, blood samples were obtained. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for circular and linear ANRIL. Age and gender were not different between the groups. Most of the parameters of the lipid profile besides creatinine and blood urea nitrogen were remarkably worse in the case group. Circular ANRIL was significantly lower in the case group while linear counterparts were significantly higher in this group. Circular/linear ratio was also significantly lower in the case group. To overcome growing devastating trend of CAD, scrutinizing different factors involved in the initiation and development of atherosclerosis is a must. Atheroprotective role of circular ANRIL and atheroprogressive role of linear ANRIL were shown in our patients with hypertension.

Abstract:: The precise and exquisite architecture of the retina is directly related to vision. Therefore, any mechanisms which are associated with disruption of retinal structure could affect on quality of vision. A large number studies indicated that several cellular and molecular processes involved in retina pathogenesis. Among different risk factors which are reported as important players in the retina diseases, deregulation of epigenetic contributors, have critical roles in the pathogenesis of these diseases. MicroRNAs (miRNAs) are a type of small non-coding RNAs that involved in various signaling pathways involved in the retina diseases. These molecules exert their function though targeting a sequence of cellular and molecular signals. Long-non coding RNAs (lncRNAs) and circular RNAs are other non-coding RNAs which can exert their regulatory roles via miRNA sponging. In this regard, it has been showed that miRNA sponging could modulate a variety of pathways in retinal diseases. Besides miRNAs, exosomes are other players in the pathogenesis of retinal diseases. Exosomes are biological vectors which could carry their cargos to recipient cells. The cargos of exosomes (i.e., proteins, lncRNAs, miRNAs, and fragments of DNA) enable to change behaviors of host cells. Here, we summarized the roles of miRNAs, miRNAs sponging and exosomes in the pathogenesis of retinal diseases.

Esophageal squamous cell carcinoma (ESCC) is the most significant subtype of esophageal cancer featured with high occurrence. Long noncoding RNAs (lncRNAs) have been proved to modulate the biological properties of cancer cells, including cell proliferation, invasion, migration, and apoptosis. LncRNA protein tyrosine phosphatase receptor type G-antisense RNA 1 (PTPRG-AS1) has been reported to play as an oncogene in diverse cancers. However, the detailed function PTPRG-AS1 may exert in ESCC is unclear.PTPRG-AS1 expression in ESCC cells was investigated via quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The effects of PTPRG-AS1 on ESCC cell proliferation, migration, glycolysis, and stemness were verified through functional assays. Mechanism assays including RIP assay, RNA pull down assay, and luciferase reporter assays were performed to verify the molecular mechanism of PTPRG-AS1.PTPRG-AS1 silencing hindered the proliferation, migration, glycolysis and stemness of ESCC cells. PTPRG-AS1 regulated pyruvate dehydrogenase kinase 1 (PDK1) expression via sponging miR-599. The PTPRG-AS1/miR-599/PDK1 axis was further verified to aggravate the progression of ESCC cells.PTPRG-AS1 sponged miR-599 to up-regulate PDK1 expression, thereby promoting the proliferation and migration as well as glycolysis and stemness properties of ESCC cells.

Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional annotation of a large number of lncRNAs. Though the number of publications related to lncRNAs has escalated in recent years, relatively few have focused on those involved in hepatic physiology and pathology. We provide an overview of evolving lncRNA classification systems and characteristics and highlight important advances in our understanding of the contribution of lncRNAs to liver disease, with a focus on nonalcoholic steatohepatitis, hepatocellular carcinoma, and cholestatic liver disease. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Background Identifying the factors affecting osteoblast differentiation ofperiodontal ligamentcells (PDLCs) can help enhance the regeneration of periodontal tissue.LncRNAplasmacytoma variant translocation 1 (lncPVT1) is an important regulatory factor involved in many biological processes, but its role in osteogenesisremains unclear. Methods Expressionsof osteogenic markers were detected by quantitative reverse transcription polymerase chain reaction and Western blot analysis. Alkaline phosphatase staining was conducted for early osteoblast differentiation and alizarin red S staining was used for mineral deposition. RNA sequencing was used to identify the miRNAs regulated by lncPVT1 during osteogenesis. Cell transfection was used to overexpress or knockdown lncPVT1 and miR-10a-5p. Dual luciferase reporter assayswere conducted to analyze the binding of miR-10a-5p to brain-derived neurotrophic factor (BDNF). Results LncPVT1 was significantly increased during osteogenic induction of PDLCs. Overexpression of lncPVT1 promoted osteogenesis, whereas lncPVT1 knockdown inhibited this process. RNA sequencing showed that miR-10a-5p expression was significantly increased after lncPVT1 knockdown.RNA immunoprecipitation assay further demonstrated the binding potential of lncPVT1 and miR-10a-5p. MiR-10a-5p inhibited the osteogenesis of PDLCs, and partially reversed the stimulatory effects of lncPVT1.Subsequently, we identified a predicted binding site for miR-10a-5p on BDNF and confirmed it using dual luciferase reporter assays. Moreover, lncPVT1 upregulated the expression of BDNF, while miR-10a-5p downregulated BDNF expression. BDNF promoted osteogenesis and partially rescued the si-lncPVT1-mediated inhibition of PDLCs osteogenic differentiation. Conclusion LncPVT1 positively regulated the osteogenic differentiation of PDLCs via miR-10a-5p and BDNF.Our resultsprovide a promising target for enhancing the osteogenic potential of PDLCs. This article is protected by copyright. All rights reserved.

Vascular dysfunction and hyperlipidemia are essential risk factors contributing to essential hypertension (EH). The plasmacytoma variant translocation 1 (PVT1) is involved in modulating angiogenesis in tumor tissues and plays an important role in fat differentiation in the progress of obesity. Therefore, we selected two tagSNPs of PVT1 (rs10956390 and rs80177647) to investigate whether they are contributing to the risk of hypertension in Chinese patients. In total, 524 adult patients with EH and 439 matched healthy controls were enrolled for two central of China. Results. PVT1 rs10956390 and rs80177647 polymorphisms were genotyped by using TaqMan assay. PVT1 rs10956390 TT genotype was associated with a decreased risk of EH ( OR = 0.561 , 95% CI = 0.372 -0.846, P = 0.006 ), while rs80177647 TA genotype was associated with an increased risk ( OR = 2.236 , 95% CI = 1.515 -3.301, P < 0.001 ). Rs10956390 T allele was associated with lower triglyceride levels in the plasma both from healthy and EH donors. What is more, there is an association between rs10956390 polymorphism and HDL-C level, as well as LDL-C. Conclusion. PVT1 rs10956390 and rs80177647 polymorphisms may contribute to the risk of EH in Chinese population by regulating blood lipid levels.

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ObjectiveGastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related mortality worldwide. The identification of valuable predictive signatures to improve the prognosis of patients with GC is becoming a realistic prospect. DNA damage response-related long noncoding ribonucleic acids (drlncRNAs) play an important role in the development of cancers. However, their prognostic and therapeutic values remain sparse in gastric cancer (GC). MethodsWe obtained the transcriptome data and clinical information from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort. Co-expression network analyses were performed to discover functional modules using the igaph package. Subsequently, lncRNA pairs were identified by bioinformation analysis, and prognostic pairs were determined by univariate analysis, respectively. In addition, we utilized least absolute shrinkage and selection operator (LASSO) cox regression analysis to construct the risk model based on lncRNA pairs. Then, we distinguished between the high- or low- risk groups from patients with GC based on the optimal model. Finally, we reevaluated the association between risk score and overall survival, tumor immune microenvironment, specific tumor-infiltrating immune cells related biomarkers, and the sensitivity of chemotherapeutic agents. Results32 drlncRNA pairs were obtained, and a 17-drlncRNA pairs signature was constructed to predict the overall survival of patients with GC. The ROC was 0.797, 0.812 and 0.821 at 1, 2, 3 years, respectively. After reclassifying these patients into different risk-groups, we could differentiate between them based on negative overall survival outcome, specialized tumor immune infiltration status, higher expressed immune cell related biomarkers, and a lower chemotherapeutics sensitivity. Compared with previous models, our model showed better performance with a higher ROC value. ConclusionThe prognostic and therapeutic signature established by novel lncRNA pairs could provide promising prediction value, and guide individual treatment strategies in the future.

Currently, early detection of lung cancer relies on the characterisation of images generated from computed tomography (CT). However, lung tissue biopsy, a highly invasive surgical procedure, is required to confirm CT-derived diagnostic results with very high false-positive rates. Hence, a non-invasive or minimally invasive biomarkers is essential to complement the existing low-dose CT (LDCT) for early detection, improve responses to a certain treatment, predict cancer recurrence, and to evaluate prognosis. In the past decade, liquid biopsies (e.g., blood) have been demonstrated to be highly effective for lung cancer biomarker discovery. In this review, the roles of emerging liquid biopsy-derived biomarkers such as circulating nucleic acids, circulating tumour cells (CTCs), long non-coding RNA (lncRNA), and microRNA (miRNA), as well as exosomes, have been highlighted. The advantages and limitations of these blood-based minimally invasive biomarkers have been discussed. Furthermore, the current progress of the identified biomarkers for clinical management of lung cancer has been summarised. Finally, a potential strategy for the early detection of lung cancer, using a combination of LDCT scans and well-validated biomarkers, has been discussed.

Background Long non-coding RNAs (lncRNAs) are essential indicators for hepatocellular carcinoma. LncRNAs can exert the same functions as their antisense mRNAs. ILF3 is an oncogene in hepatocellular carcinoma. ILF3 divergent transcript (ILF3-AS1) is the antisense RNA of ILF3, and has been reported as an oncogene in various cancers. Aims To explore the role of lncRNA ILF3-AS1 in malignant phenotypes of hepatocellular carcinoma cells. Methods and results RT-qPCR analysis revealed that ILF3-AS1 was significantly upregulated in hepatocellular carcinoma cells. The hepatocellular carcinoma cell viability was suppressed by silenced ILF3-AS1. Transwell and wound healing assays showed that ILF3-AS1 downregulation inhibited cell invasion and migration. The levels of proteins associated with epithelial-mesenchymal transition (EMT) process and the Notch pathway were detected by western blot analysis. Luciferase reporter, RNA pull down and RIP assays were used to investigate the relationship between ILF3-AS1 and downstream target genes. ILF3-AS1 competed with meis homeobox 2 (MEIS2) for miR-628–5p in hepatocellular carcinoma cells. ILF3-AS1 elevated the levels of key proteins on the Notch pathway. Rescue assays demonstrated that MEIS2 reversed the antitumor effects of silenced ILF3-AS1 on hepatocellular carcinoma. In vivo assays demonstrated that ILF3-AS1 silencing inhibited the hepatocellular carcinoma tumor growth. Conclusions ILF3-AS1 promoted hepatocellular carcinoma progression via the Notch pathway and miR-628–5p/MEIS2 axis.

Background Long non-coding RNAs (lncRNAs) are involved in the development of hepatocellular carcinoma (HCC). We aimed to investigate the function of LINC01146 in HCC. Methods The expression of LINC01146 in HCC tissues was explored via The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and was verified using quantitative real-time polymerase chain reaction (qRT–PCR) in our HCC cohort. Kaplan–Meier analysis was used to assess the relationship between LINC01146 and the prognosis of HCC patients. Cell Counting Kit 8, colony formation assays, Transwell assays, flow cytometric assays, and tumour formation models in nude mice were conducted to reveal the effects of LINC01146 on HCC cells both in vitro and in vivo. Bioinformatic methods were used to explore the possible potential pathways of LINC01146 in HCC. Results LINC01146 was significantly decreased in HCC tissues compared with adjacent normal tissues and was found to be related to the clinical presentations of malignancy and the poor prognosis of HCC patients. Overexpression of LINC01146 inhibited the proliferation, migration, and invasion of HCC cells in vitro, while promoting their apoptosis. In contrast, downregulation of LINC01146 exerted the opposite effects on HCC cells in vitro. In addition, overexpression of LINC01146 significantly inhibited tumour growth, while downregulation of LINC01146 promoted tumour growth in vivo. Furthermore, the coexpressed genes of LINC01146 were mainly involved in the “metabolic pathway” and “complement and coagulation cascade pathway”. Conclusion LINC01146 expression was found to be decreased in HCC tissues and associated with the prognosis of HCC patients. It may serve as a cancer suppressor and prognostic biomarker in HCC.

Objective Oral squamous cell carcinoma (OSCC) is a malignant tumor. This study aimed to investigate the role of a long noncoding RNA (lncRNA), LINC01123, in OSCC prognosis and progression and to explore the underlying mechanisms. Study Design OSCC tissues were collected from 102 patients, and 4 OSCC cell lines were analyzed. The expression levels of LINC01123 and miR-34a-5p were estimated using quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) and Transwell assays were used to assess the proliferation, migration, and invasion of OSCC cells. Kaplan-Meier survival analysis was used to analyze the prognostic value of LINC01123 in OSCC. Results The analysis results showed that LINC01123 was overexpressed in OSCC tumor tissues; also, the prognosis of patients with OSCC with high LINC01123 expression levels was poor. The knockdown of LINC01123 inhibited the proliferation, migration, and invasion of OCSS cells. MiR-34a-5p was a target of LINC01123, and its inhibitor could reverse the effect of silenced LINC01123 on the progression of OSCC. Conclusions Highly expressed LINC01123 was associated with poor prognosis of OSCC and regulated OSCC cell proliferation, invasion, and migration by sponging miR-34a-5p. Therefore, the LINC01123/miR-34a-5p axis may provide new ideas for the prognosis and treatment of OSCC.