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Abstract Prostate cancer (PCa) ranks as the second most prevalent cancer among males globally. However, the exact mechanisms underlying its progression remain inadequately elucidated. The present study sought to investigate the role and underlying molecular mechanism of hsa_circ_0001671 (circ_0001671) in the pathogenic behavior of PCa cells. Guided by the ceRNA theory, miR-27b-3p was employed to identify circRNAs that could potentially regulate Bloom Syndrome Protein (BLM). A series of experimental approaches including bioinformatics, luciferase assays, Fluorescent In Situ Hybridization (FISH), RNA-pulldown, and RNA Immunoprecipitation (RIP) were utilized to validate the miRNA sponge function of circ_0001671. Divergent primer PCR, RNase R treatments, and Sanger sequencing were conducted for the identification of circ_0001671. Quantitative RT-PCR and Western blot analyses were performed to validate gene expression levels. Both in vitro and in vivo experiments were conducted to assess the functional role of circ_0001671 in PCa cells.It was observed that the expression levels of circ_0001671 and BLM were significantly elevated in PCa tissues and cell lines, whereas miR-27b-3p showed decreased expression. Circ_0001671 was found to promote cellular proliferation, migration, and invasion, while inhibiting apoptosis. In vivo assays confirmed that circ_0001671 facilitated tumor growth. Further mechanistic studies revealed that circ_0001671 acted as a competing endogenous RNA (ceRNA) for BLM by sponging miR-27b-3p. The oncogenic role of circ_0001671 in PCa was shown to be modulated through the miR-27b-3p/BLM axis. In conclusion, circ_0001671 exerts an oncogenic effect in prostate cancer through the regulation of BLM by sponging miR-27b-3p, thus suggesting a novel molecular target for the treatment of PCa.

Prostate cancer (PCa) ranks as the second most prevalent cancer among males globally. However, the exact mechanisms underlying its progression remain inadequately elucidated. The present study sought to investigate the role and underlying molecular mechanism of hsa_circ_0001671 (circ_0001671) in the pathogenic behavior of PCa cells. Guided by the ceRNA theory, miR-27b-3p was employed to identify circRNAs that could potentially regulate Bloom Syndrome Protein (BLM). A series of experimental approaches including bioinformatics, luciferase assays, Fluorescent In Situ Hybridization (FISH), RNA-pulldown, and RNA Immunoprecipitation (RIP) were utilized to validate the miRNA sponge function of circ_0001671. Divergent primer PCR, RNase R treatments, and Sanger sequencing were conducted for the identification of circ_0001671. Quantitative RT-PCR and Western blot analyses were performed to validate gene expression levels. Both in vitro and in vivo experiments were conducted to assess the functional role of circ_0001671 in PCa cells.It was observed that the expression levels of circ_0001671 and BLM were significantly elevated in PCa tissues and cell lines, whereas miR-27b-3p showed decreased expression. Circ_0001671 was found to promote cellular proliferation, migration, and invasion, while inhibiting apoptosis. In vivo assays confirmed that circ_0001671 facilitated tumor growth. Further mechanistic studies revealed that circ_0001671 acted as a competing endogenous RNA (ceRNA) for BLM by sponging miR-27b-3p. The oncogenic role of circ_0001671 in PCa was shown to be modulated through the miR-27b-3p/BLM axis. In conclusion, circ_0001671 exerts an oncogenic effect in prostate cancer through the regulation of BLM by sponging miR-27b-3p, thus suggesting a novel molecular target for the treatment of PCa. [ABSTRACT FROM AUTHOR]

The adenopituitary secretes follicle‐stimulating hormone (FSH), which plays a crucial role in regulating the growth, development, and reproductive functions of organisms. Investigating the process of FSH synthesis and secretion can offer valuable insights into potential areas of focus for reproductive research. Epidermal growth factor (EGF) is a significant paracrine/autocrine factor within the body, and studies have demonstrated its ability to stimulate FSH secretion in animals. However, the precise mechanisms that regulate this action are still poorly understood. In this research, in vivo and in vitro experiments showed that the activation of epidermal growth factor receptor (EGFR) by EGF induces the upregulation of miR‐27b‐3p and that miR‐27b‐3p targets and inhibits Foxo1 mRNA expression, resulting in increased FSH synthesis and secretion. In summary, this study elucidates the precise molecular mechanism through which EGF governs the synthesis and secretion of FSH via the EGFR/miR‐27b‐3p/FOXO1 pathway. [ABSTRACT FROM AUTHOR]

Despite advances in multiple myeloma (MM) treatment, drug resistance remains a clinical challenge. We aimed to develop a prognostic model for bortezomib resistance based on miRNA expression profiling. The study included 40 previously untreated MM patients receiving bortezomib-based regimens (20 treatment-sensitive, 20 resistant). Pretreatment venous blood samples were analyzed for miRNA expression. Differential expression analysis revealed upregulated miR-27b-3p (FC 1.45, p = 0.017) and let-7b-5p (FC 1.44, p = 0.025) in the resistant group. Univariate analysis identified let-7b-5p (OR 3.17, 95%CI: 1.19–11.4, p = 0.04) and miR-27b-3p (OR 4.73, 95%CI: 1.4–26.6, p = 0.036) as risk factors for resistance. The final multivariate model included miR-27b-3p (OR 23.1, 95% CI: 2.8–452, p = 0.015), let-7b-5p (OR 4.38, 95% CI: 1.28–22.2, p = 0.038), and miR-103a-3p (OR 15.3, 95% CI: 1.33–351, p = 0.049). These miRNAs may serve as biomarkers of treatment response in MM. However, external validation is necessary to confirm the clinical utility of our model. [ABSTRACT FROM AUTHOR]

Abstract Lysyl oxidase-like 2 (LOXL2) is an extracellular copper-dependent enzyme that plays a central role in fibrosis by catalyzing the crosslinking and deposition of collagen. Therapeutic LOXL2 inhibition has been shown to suppress liver fibrosis progression and promote its reversal. This study investigates the efficacy and underlying mechanisms of human umbilical cord-derived exosomes (MSC-ex) in LOXL2 inhibition of liver fibrosis. MSC-ex, nonselective LOX inhibitor β-aminopropionitrile (BAPN), or PBS were administered into carbon tetrachloride (CCl4)-induced fibrotic livers. Serum LOXL2 and collagen crosslinking were assessed histologically and biochemically. MSC-ex’s mechanisms on LOXL2 regulation were investigated in human hepatic stellate cell line LX-2. We found that systemic administration of MSC-ex significantly reduced LOXL2 expression and collagen crosslinking, delaying the progression of CCl4-induced liver fibrosis. Mechanically, RNA-sequencing and fluorescence in situ hybridization (FISH) indicated that miR-27b-3p was enriched in MSC-ex and exosomal miR-27b-3p repressed Yes-associated protein (YAP) expression by targeting its 3ʹ untranslated region in LX-2. LOXL2 was identified as a novel downstream target gene of YAP, and YAP bound to the LOXL2 promoter to positively regulate transcription. Additionally, the miR-27b-3p inhibitor abrogated the anti-LOXL2 abilities of MSC-ex and diminished the antifibrotic efficacy. miR-27b-3p overexpression promoted MSC-ex mediated YAP/LOXL2 inhibition. Thus, MSC-ex may suppress LOXL2 expression through exosomal miR-27b-3p mediated YAP down-regulation. The findings here may improve our understanding of MSC-ex in liver fibrosis alleviation and provide new opportunities for clinical treatment.

ABSTRACT: Stress-induced immunosuppression (SIIS) is one of the common problems in intensive poultry production, which often reduces the prevention and control effects of various vaccines, including infectious bursal disease virus (IBDV) vaccine, and brings enormous economic losses to the poultry industry. However, the molecular mechanisms of SIIS inhibiting immune response to IBDV vaccine remain unclear. In this study, suppressor of cytokine signaling 3 (SOCS3) gene was selected and stress-induced immunosuppressed chickens were simulated using dexamethasone (Dex). Quantitative real-time PCR (qRT-PCR) was conducted to analyze its expression characteristics and game relationships between SOCS3 gene and miR-27b-3p (it could target SOCS3 gene) in the process of SIIS inhibiting immune response to IBDV vaccine in chicken, and the potential application value of circulating miR-27b-3p as a biomarker was also identified. The results showed that SOCS3 gene and miR-27b-3p were significantly differentially expressed in the candidate tissues during SIIS inhibiting the immune response to IBDV (P < 0.05), respectively, which were key factors involved in the process. Moreover, miR-27b-3p and SOCS3 gene showed game regulation relationships in several tissues during the process, so the miR-27b-3p/SOCS3 regulatory network was one of the key mechanisms of SOCS3 gene participating in the process. Circulating miR-27b-3p was differentially expressed in serum at 10 time points (1, 2, 3, 4, 5, 7, 14, 21, 28, and 35 days postimmunization (dpi)) in the process (P < 0.05), showing that circulating miR-27b-3p was a valid candidate target as a molecular marker for detecting SIIS inhibiting the IBDV immune response. This study can provide references for further studying molecular mechanisms of stress affecting immune response.

Lysyl oxidase-like 2 (LOXL2) is an extracellular copper-dependent enzyme that plays a central role in fibrosis by catalyzing the crosslinking and deposition of collagen. Therapeutic LOXL2 inhibition has been shown to suppress liver fibrosis progression and promote its reversal. This study investigates the efficacy and underlying mechanisms of human umbilical cord-derived exosomes (MSC-ex) in LOXL2 inhibition of liver fibrosis. MSC-ex, nonselective LOX inhibitor β-aminopropionitrile (BAPN), or PBS were administered into carbon tetrachloride (CCl4)-induced fibrotic livers. Serum LOXL2 and collagen crosslinking were assessed histologically and biochemically. MSC-ex's mechanisms on LOXL2 regulation were investigated in human hepatic stellate cell line LX-2. We found that systemic administration of MSC-ex significantly reduced LOXL2 expression and collagen crosslinking, delaying the progression of CCl4-induced liver fibrosis. Mechanically, RNA-sequencing and fluorescence in situ hybridization (FISH) indicated that miR-27b-3p was enriched in MSC-ex and exosomal miR-27b-3p repressed Yes-associated protein (YAP) expression by targeting its 3ʹ untranslated region in LX-2. LOXL2 was identified as a novel downstream target gene of YAP, and YAP bound to the LOXL2 promoter to positively regulate transcription. Additionally, the miR-27b-3p inhibitor abrogated the anti-LOXL2 abilities of MSC-ex and diminished the antifibrotic efficacy. miR-27b-3p overexpression promoted MSC-ex mediated YAP/LOXL2 inhibition. Thus, MSC-ex may suppress LOXL2 expression through exosomal miR-27b-3p mediated YAP down-regulation. The findings here may improve our understanding of MSC-ex in liver fibrosis alleviation and provide new opportunities for clinical treatment. [ABSTRACT FROM AUTHOR]

Cisplatin is one of the most effective chemotherapeutic agents strongly associated with nephrotoxicity. Tubular adult renal progenitor cells (tARPC) can regenerate functional tubules and participate in the repair processes after cisplatin exposition. This study investigated the molecular mechanisms underlying the protective effect of tARPC on renal epithelium during cisplatin nephrotoxicity. By performing a whole-genome transcriptomic analysis, we found that tARPC, in presence of cisplatin, can strongly influence the gene expression of renal proximal tubular cell [RPTEC] by inducing overexpression of CYP1B1, a member of the cytochrome P450 superfamily capable of metabolizing cisplatin and of hypoxia/cancer-related lncRNAs as MIR210HG and LINC00511. Particularly, tARPC exerted renoprotection and regeneration effects via extracellular vesicles (EV) enriched with CYP1B1 and miR-27b-3p, a well-known CYP1B1 regulatory miRNA. The expression of CYP1B1 by tARPC was confirmed by analyzing biopsies of cisplatin-treated renal carcinoma patients that showed the colocalization of CYP1B1 with the tARPC marker CD133. CYP1B1 was also overexpressed in urinary EV purified from oncologic patients that presented nephrotoxicity episodes after cisplatin treatment. Interestingly CYP1B1 expression significantly correlated with creatinine and eGFR levels. Taken together, our results show that tARPC are able to counteract cisplatin-induced nephrotoxicity via CYP1B1 release through EV. These findings provide a promising therapeutic strategy for nephrotoxicity risk assessment that could be related to abundance of renal progenitors. [ABSTRACT FROM AUTHOR]

Objective：To investigate the effect of miR⁃27b⁃3p on osteosarcoma cells growth and its potential molecular mechanism. Methods：①The expression of miR⁃27b⁃3p in osteosarcoma cell lines was analyzed by RT⁃qPCR. ②CCK⁃8 assay, colony formation assay and flow cytometry analysis were used to detect the effect of miR⁃27b⁃3p and structure⁃specific recognition protein⁃1（SSRP1）on osteosarcoma cell growth. ③The miRNA target prediction database was used to predict potential target gene of miR⁃27b⁃3p, and dual luciferase reporter assay was performed to demonstrate the relationship of miR⁃27b⁃3p and its target genes. ④Efficiency of knockdown or overexpression was validated by Western blot analysis. Results：①The expression of miR ⁃27b ⁃3p in osteosarcoma cell lines and clinical samples was low, and overexpression of miR⁃27b⁃3p inhibited the growth of osteosarcoma cells. ②Bioinformatics analysis and dual⁃fluorescence reporter assay confirmed that SSRP1 was a target gene of miR⁃27b⁃3p, and the expression of SSRP1 was regulated by miR⁃27b⁃3p. ③Silencing of SSRP1 significantly inhibited cell proliferation and increased cell apoptosis of osteosarcoma cells. ④Overexpression of SSRP1 partly reversed the inhibitory effect of miR⁃27b⁃3p on osteosarcoma cell growth. Conclusion：miR⁃27b⁃3p is low expressed in osteosarcoma cells, and it regulates the growth of osteosarcoma cells by targeting SSRP1. Targeting the miR⁃27b⁃3p/ SSRP1 axis may become a new therapeutic strategy for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is a common childhood cancer. Circular RNA RAN binding protein 17 (circRANBP17) has been identified to participate in diverse tumor progression. This study aims to explore the function and mechanism of circRANBP17 in NB. The levels of circRANBP17, miR-27b-3p and KDM1A in NB tissues and cells were measured by qRT-PCR. Mouse model assay was performed to investigate the effect of circRANBP17 knockdown on tumor formation in vivo. The levels of circRANBP17 and KDM1A were significantly up-regulated, and the level of miR-27b-3p was strikingly down-regulated in NB tissues and cells (SK-N-SH and SK-N-AS). Functional studies indicated that miR-27b-3p inhibitor mitigated the inhibitory effects on cell proliferation, migration, invasion and the promoting effect on cell apoptosis in SK-N-SH and SK-N-AS cells induced by circRANBP17 knockdown. Also, miR-27b-3p regulated NB cell malignancy by targeting KDM1A. Further studies revealed that miR-27b-3p inhibitor reversed the low expression of KDM1A induced by circRANBP17 knockdown. In support, circRANBP17 knockdown led to inhibition of tumor formation in vivo. In conclusion, circRANBP17 modulated KDM1A to promote cell proliferation, migration, invasion and restrain cell apoptosis in NB by sponging miR-27b-3p, and the new regulatory network may provide a theoretical basis for the further study of NB.

Neuroblastoma (NB) is a common childhood cancer. Circular RNA RAN binding protein 17 (circRANBP17) has been identified to participate in diverse tumor progression. This study aims to explore the function and mechanism of circRANBP17 in NB. Thelevels of circRANBP17, miR-27b-3p and KDM1A in NB tissues and cells were measured by qRTPCR. Mouse model assay was performed to investigate the effect of circRANBP17 knockdown on tumor formation in vivo. The levels of circRANBP17 and KDM1A were significantly up-regulated, and the level of miR-27b-3p was strikingly down-regulated in NB tissues and cells (SK-N-SH and SK-N-AS). Functional studies indicated that miR-27b-3p inhibitor mitigated the inhibitory effects on cell proliferation, migration, invasion and the promoting effect on cell apoptosis in SK-N-SH and SK-N-AS cells induced by circRANBP17 knockdown. Also, miR-27b-3p regulated NB cell malignancy by targeting KDM1A. Further studies revealed that miR-27b-3p inhibitor reversed the low expression of KDM1A induced by circRANBP17 knockdown. In support, circRANBP17 knockdown led to inhibition of tumor formation in vivo. In conclusion, circRANBP17 modulated KDM1A to promote cell proliferation, migration, invasion and restrain cell apoptosis in NB by sponging miR-27b-3p, and the new regulatory network may provide a theoretical basis for the further study of NB. [ABSTRACT FROM AUTHOR]

Summary: Non-medical use of ketamine as an adulterant to ecstasy is more prevalent than amphetamine in Taiwan. Ketamine's effect on immunosuppression might play some functional role in tumor growth, while it is still controversial whether ketamine abuse could increase tumor growth or not. This study aimed to investigate the influence of ketamine addiction in breast tumors and related gene expressions. The effect of ketamine treatment on proliferation, colony formation, migration, and invasion of triple-negative breast cancer cell line EO771 was examined. In addition, a ketamine addiction mice model was established by intraperitoneal injection (IP) of ketamine in mice and used to investigate the effects of ketamine addiction on tumor growth and the possible mechanisms. In the in vitro studies, ketamine treatment at different concentrations did not affect EO771 cell proliferation and colony formation. But ketamine did enhance migration and invasion of EO771 cells. The in vivo experiments showed significantly increased breast tumor volume and weight in ketamine-addicted mice than in normal saline groups. miR-27b-3p level, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) significantly increased in tumors of ketamine addiction mice compared to control mice. In vivo evidence showed that Ketamine might increase tumor growth on the tumor microenvironment, and miR-27b-3p, HER2, and EGFR might play a role in the process. [ABSTRACT FROM AUTHOR]

Tendon injuries are common clinical issues resulted from tissue overuse and age-related degeneration. Previous sutdies have suggested that exosomes secreted by mesenchymal stem cells (MSCs) contribute to tissue injury repair. Here, we provide evidence for a critical role of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes in reducing tendon injury by activating the RhoA signaling. Treatment of primary injured tenocytes with hucMSC exosomes increases cell proliferation and invasion, which correlates with increased RhoA activity. RhoA mediates the effects of hucMSC exosomes, as treatment of primary injured tenocytes with the RhoA inhibitor, CCG-1423, abolishes the effects of hucMSC exosomes on cell proliferation and invasion. Mechanistically, we observe that hucMSC exosomes induce the expression of a microRNA, miR-27b-3p, which targets and suppresses ARHGAP5, a negative regulator of RhoA. Consistent with this observation, ARHGAP5 overexpression suppresses the effects of hucMSC exosomes on cell proliferation and invasion, while knockdown of ARHGAP5 rescues these effects. Finally, we demonstrate the functional significance of our findings in vivo using an Achilles tendon injury model and show that treatment with exosomes reduces tendon injury in rats, which correlates with increased RhoA activity and reduced ARHGAP5 expression. Taken together, our findings highlight a critical role of hucMSC exosomes in reducing tendon injury via miR-27b-3p-mediated suppression of ARHGAP5, resulting in RhoA activation, and leading to increased cell proliferation and invasion of primary injured tenocytes.

Glioma-associated oncogene homolog 1 (GLI1), a zinc-finger transcription factor, is upregulated in tumors and promotes cancer cell proliferation and migration. However, whether GLI1 involves in pulmonary artery smooth muscle cells (PASMCs) proliferation and migration and the detailed molecular mechanisms underlying GLI1 in pulmonary arterial hypertension (PAH) are not yet clear. Primary cultured rat PASMCs and monocrotaline (MCT)-induced PAH rats model were applied to address these issues in the present study. We found that the expression of GLI1 was significantly increased in endothelin-1 (ET-1) treated PASMCs, accompanied with the activation of microRNA (miR)-27b-3p/F-box and WD repeat domain containing 7 (FBXW7)/kruppel-like factor 5 (KLF5)/GLI1 pathway through endothelin-1 receptor type A (ETAR). Elevated miR-27b-3p suppressed FBXW7 expression, which led to KLF5 accumulation by decreasing its ubiquitinated degradation, KLF5 further induced GLI1 upregulation leading to PASMCs proliferation and migration. In addition, in MCT-induced PAH rats, targeting ETAR/miR-27b-3p/FBXW7/KLF5/GLI1 pathway effectively prevented the pulmonary vascular remodeling and the development of PAH in rats. Our study indicates that interfering ETAR/miR-27b-3p/FBXW7/KLF5/GLI1 signaling axis might have a potential value in the prevention and treatment of PAH. [Display omitted] • Increased GLI1 contributes to PASMCs proliferation and migration. • The miR-27b-3p/FBXW7/KLF5 axis mediates GLI1 upregulation in PAH. • Inhibiting ETAR/miR-27b-3p/FBXW7/KLF5/GLI1 pathway benefit PAH. [ABSTRACT FROM AUTHOR]

Objective To investigate the serum expression characteristics of miR-27b-3p and miR-342-3p in type 2 diabetic nephropathy (DN) patients and the diagnostic value for DN. Methods A total of 157 patients with DN were selected and divided into the normal albuminuria group (NA group, n=49), the microalbuminuria group (MA group, n=41) and the macroalbuminuria group (DN group, n=67) according to the ratio of albumin to creatinine (UACR) of urine specimens. Clinical data and the expression of serum miR-27b-3p and miR-342-3p, renal function and urinary fibrosis indicators were detected by real-time quantitative polymerase chain reaction. Blood urea nitrogen (BUN) and blood creatinine (Scr), were detected by automatic biochemical analyzer. Urine type Ⅳ collagen (Ⅳ-C), laminin (LN) and type Ⅲ procollagen peptide (PCⅢ) were detected by double-antibody sandwich enzyme-linked immunosorbent assay. The factors influencing the pathogenesis of DN and the diagnostic value of miR-27b-3p and miR-342-3p for DN were analyzed. Results Compared with the NA group, the levels of HbA1c, UACR, urinary Ⅳ-C, urinary LN and urinary PCⅢ were increased, while the expresson levels of miR-27b-3p and miR-342-3p were decreased in the DN group and the MA group (P＜0.05). Levels of BUN and Scr were increased in the DN group (P＜0.05), and eGFR level decreased (P＜0.05). The higher level of urinary PCⅢ was a risk factor for DN, while the higher levels of miR-27b-3p, miR-342-3p and eGFR were protective factors of DN (P＜0.05). The expressions levels of miR-27b-3p and miR-342-3p were positively correlated with eGFR (r = 0.647, 0.661, P＜0.05) and negatively correlated with urinary PCⅢ (r=-0.739, P＜0.05). The area under the curve for diagnosing DN by combining eGFR, urinary PCⅢ, miR-27b-3p and miR-342-3p was higher than that of eGFR, urinary PCⅢ, miR-27b-3p, miR-342-3p alone (Z=5.631, 5.794, 6.715, 4.577, P＜0.05). Conclusion The decreased expressions of serum miR-27b-3p and miR-342-3p are associated with decreased renal function and DN occurrence in patients with type 2 diabetes, which can be used as biological indicators for the auxiliary diagnosis of DN. [ABSTRACT FROM AUTHOR]

Eating during a rest phase disrupts the biological clock system and leads to obesity and metabolic diseases. Although a rest phase restricted feeding (RF) is reported to enhance hepatic lipid accumulation, the mechanism(s) of the phenomenon is still unknown. This study evaluated the potential involvement of the CD36-related transport of lipids into the liver in mice with the RF procedure. This study showed that hepatic lipid accumulation was more significant in the RF group compared with mice under an active phase restricted feeding (AF). The RF procedure also elevated the expression of CD36 mRNA and its protein on the cellular membrane throughout the day. The transcription factor profiling array revealed that the RF activated the proliferator-activated receptor-γ (PPARγ), one of the CD36 transcript enhancers. In the liver of RF mice, the expression of miR-27b-3p, which is known to interfere with PPARγ gene expression, significantly decreased. These results suggest that the RF procedure inhibits the expression of miR-27b-3p in the liver and subsequently elevates PPARγ activity. Activated PPARγ might lead to CD36 upregulation, which, in turn, stimulates the transport of lipids into the liver. [ABSTRACT FROM AUTHOR]

Objectives: Epilepsy is a neurological disease that pathologically affects brain functions. The epileptic hippocampus has modified microRNA(miRNA) levels. Therefore, we aimed to evaluate the neuroprotective effect of thymoquinone (TQ) in PTZ-induced epilepsy and to demonstrate the overlap between miRNA and mRNA expression profiles. Methods: Male adult Wistar albino rats (200–230 g, n = 20) were divided into three groups as control (n = 6), PTZ (n = 7), and TQ + PTZ (n = 7). The PTZ kindling model was created by injecting PTZ in sub convulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, and 24 of the study into animals. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the TQ+PTZ group were treated by oral gavage with a 20 mg/kg TQ 2 h before each PTZ injection. The rats in the control group were treated with 0.5 ml saline. Seizure severity was evaluated with the Racine scale. The genes and signaling pathways targeted by miRNAs were determined by bioinformatics analysis. Results: In the rat hippocampus, mature 728 miRNAs were analyzed by microarray and the nine miRNA were verified by quantitative Real-Time PCR. rno-miR-182 and rno-miR-27b-3p were up-regulated in the PTZ group and down-regulated in the TQ + PTZ group. Discussion: In the PTZ kindling epilepsy model, the expression of these two miRNAs was regulated by TQ and exerted a neuroprotective effect by controlling the activities of target genes. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are important mediators in esophageal squamous cell carcinoma (ESCC) carcinogenesis. We aim to explore the functions and mechanisms of circLONP2 in ESCC progression. The circLONP2 level was evaluated in ESCC samples and cell lines. The role and mechanisms of circLONP2 in ESCC proliferation and migration were demonstrated in vitro. We found that circLONP2 was upregulated in human ESCC and predicts poor overall survival (OS) and disease-free survival (DFS). CircLONP2 promotes ESCC aggressiveness by directly interacting with miR-27b-3p, thus upregulating the expression levels of its target gene ZEB1 by suppressing miR-27b-3p activity. Therefore, we demonstrated that circLONP2/miR-27b-3p/ZEB1 axis promotes ESCC metastasis via regulating epithelial-to-mesenchymal transition (EMT)-related proteins. CircLONP2 may serve as an oncogenic circRNA and as a prognostic biomarker in ESCC progression. [ABSTRACT FROM AUTHOR]

Background and Aims: Evidence suggests that interferon alpha (IFNα) plays an essential role in decreasing the HBsAg quantification and elevating the rate of clinical cure in chronic hepatitis B (CHB). However, the mechanisms underlying the effects of the exosomes on the expression of host genes in IFNα treatment remain unclear. Methods: CHB patients with IFNα treatment were divided into responders and non‐responders according to the degree of HBsAg decline. Through microRNA sequencing and a series of molecular biology methods, the key microRNAs in serum exosomes associated with clinical antiviral response of Peg‐IFNα treatment in nucleotide analogue‐treated CHB patients were investigated. The roles of exosomal miRNAs on the IFNα signal pathway were explored in macrophages. Results: MicroRNA sequencing and RT‐qPCR assays confirmed six distinctly declined miRNAs in serum exosomes of responders at week 12 compared with levels at baseline. Exosomes with declined miR27b‐3p in the serum of Peg‐IFNα‐treated responders activated phosphorylation of interferon regulatory factor 3/7 (IRF3/7) in IFNα synthesis pathway in macrophages. However, miR27b‐3p overexpression in HepAD38 cells suppressed IFNα synthesis in macrophages, resulting in insufficient ability to eliminate HBV, whereas the inhibitory effect could be blocked by inhibitors of exosomes release. Luciferase assay showed miR‐27b‐3p directly suppressed retinoic acid‐inducible gene I (RIG‐I) and TANK‐binding kinase 1 (TBK1) expressions, and these effects could be abrogated in mutation experiments. Conclusions: In IFNα treatment, exosomes with declined miR‐27b‐3p triggered activation of RIG‐I/TBK1 signalling in macrophages against HBV. Serum exosomal miR‐27‐3p might represent a potential biomarker for patients with CHB. [ABSTRACT FROM AUTHOR]

Introduction: Glioma is a collective term for tumors derived from glial cells and neuronal cells in the nervous system, and is the most common malignant tumor in the brain. Nowadays, the problem of poor treatment effect and high recurrence rate of patients remains to be solved. Material and methods: In this study, the expression levels of LINC01128 in glioma tissues, cells, and normal control group were determined by real-time quantitative PCR (RT-qPCR). Kaplan-Meier curve was used to evaluate the prognosis and survival. Multivariate Cox analysis was chosen to estimate the prognostic risk factors of glioma. Cell counting kit-8 (CCK-8) and Transwell methods were used to detect the effect of silencing LINC01128 on the proliferation, migration, and invasion of glioma cells, and the targeting effect of LINC01128 on miR-27b-3p was determined based on bio-informatics analysis and luciferase activity detection. Results: LINC01128 was up-regulated in glioma tissues and cells. The possibility of LINC01128 as a prognostic factor of glioma was obtained through Kaplan-Meier's clinical data analysis and multivariate Cox analysis. Silencing LINC01128 targeting miR-27b-3p inhibited the proliferation, migration, and invasion activity of glioma cells. Moreover, there was a negative correlation between LINC01128 and miR-27b-3p. Conclusions: Silencing LINC01128 inhibited the proliferation, migration, and invasion levels of glioma cells by targeting miR-27b-3p, thereby affecting the progression of gliomas. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. Methods: GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. Cell apoptosis was determined using flow cytometry assay. Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). Results: miR-27b-3p was markedly downregulated in HG-treated GC-1 spg cells. HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. miR-27b-3p directly bound to Gfpt1 and negatively regulated its expression. Conclusion: miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage. [ABSTRACT FROM AUTHOR]

Purpose: Catenin Beta 1 (CTNNB1) is a key regulator of cell proliferation and invasion in endometriosis; however, its upstream factor is not clear. Long noncoding RNAs may participate in endometriosis. The aim of this study was to investigate the mechanism of interaction between LINC02381 and CTNNB1 in endometriosis. Method: Screening and validation of RNAs were completed by whole transcriptional sequencing and qRT-PCR. The subcellular localization of LINC02381 was determined by RNA in situ hybridization and nucleo-cytoplasmic separation. Plasmids were transfected for functional experiments. Luciferase assay was used to verify the binding relationship. Results: The expression of LINC02381 and CTNNB1 was significantly increased in ovarian ectopic endometrial tissues (OSAs) and ectopic endometrial stromal cells (ESCs). When LINC02381 was downregulated in ESCs, the expression of CTNNB1, metallopeptidase 9 (MMP9) and cyclinD1, as well as ESCs invasion and proliferation, decreased. LINC02381 was mainly present in the cytoplasm of ESCs, indicating that it may act as a competitive endogenous RNA. Bioinformatic analysis revealed that microRNA-27b-3p (miR-27b-3p) is a downstream target of LINC02381. miR-27b-3p decreased in OSAs and ESCs. Moreover, when miR-27b-3p was upregulated in ESCs, the expression of CTNNB1, MMP9 and cyclinD1, as well as the invasion and proliferation ability of ESCs, were reduced. Additionally, rescue experiments demonstrated that the expression of CTNNB1, MMP9 and cyclinD1, as well as the invasion and proliferation ability, were significantly increased in the group transfected with both sh-LINC02381 and a miR-27b-3p inhibitor. Conclusion: LINC02381 upregulated CTNNB1 by adsorbing miR-27b-3p, causing increased proliferation and invasion of ESCs. [ABSTRACT FROM AUTHOR]

Abstract Background Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) exhibits an oncogenic role in multiple cancers, including gastric cancer (GC). But, the functions of NEAT1 in modulating radio-sensitivity of GC and its potential molecular mechanisms have not been totally elucidated. Methods qRT-PCR was performed to detect the expressions of NEAT1 and microRNA-27b-3p (miR-27b-3p). Kaplan–Meier survival curves for NEAT1 expression in GC created using KM Plotter. Colony formation assay was used to determine the survival fraction. Cell apoptosis was evaluated by flow cytometry. Luciferase reporter assay was used to verify the relationship between miR-27b-3p and NEAT1. Results NEAT1 was highly expressed while miR-27b-3p was downregulated in GC tissues and cells. NEAT1 was negatively correlated with that of miR-27b-3p and associated with poor overall survival. Moreover, NEAT1 and miR-27b-3p varied inversely after radiation in GC tissues and cells. Loss of NEAT1 or upregulation of miR-27b-3p increased the effect of radiation on cell survival fraction inhibition and apoptosis promotion. In addition, NEAT1 negatively regulated the expression of miR-27b-3p in GC cells. Interestingly, the depletion of miR-27b-3p dramatically attenuated the NEAT1 knockdown-mediated function in AGS and MKN-45 cells treated with radiation in vitro. Similarly, downregulation of NEAT1 enhanced the radiation-mediated inhibition of tumor growth, which was mitigated by decrease of miR-27b-3p. Conclusion NEAT1 depletion enhanced radio-sensitivity of GC by negatively regulating miR-27b-3p in vitro and in vivo.

Atherosclerosis in diabetes is a leading cause of cardiovascular complications. Intermedin (IMD) is a calcitonin peptide that is known to inhibit macrophage phagocytosis in atherosclerosis, but the exact mechanism is unclear. We investigate genes that are differentially expressed in response to IMD in hyperglycemic conditions and determine whether they delay the progression of atherosclerosis. An atherosclerotic and diabetic-murine model was generated in 8-week-old male ApoE−/− mice receiving streptozotocin and a high-fat diet. The mouse model was treated with IMD and the expression levels of NF-κB, Dnm3os, miR-27b-3p, and SLAMF7 were detected in plaque tissue and macrophages cultured with high glucose concentrations. Phagocytosis was determined by oxidized-low-density lipoprotein (Ox-LDL) uptake and the interactions among Dnm3os, SLAMF7 and miR-27b-3p were assessed by dual-luciferase reporter assays. The expression of NF-κB, Dnm3os, and SLAMF7 was enhanced in atherosclerotic plaques but decreased by IMD. The suppression of Dnm3os reduced plaque formation in IMD-treated mice even further whereas increased by miR-27b-3p. Dnm3os and SLAMF7 were competitively bind to miR-27b-3p in vivo. In vitro , ox-LDL uptake is elevated in macrophages cultured in hyperglycemic conditions but reduced by IMD. Dual-luciferase assays indicate that Dnm3os positively regulates SLAMF7 through miR-27b-3p expression. In conclusion, Dnm3os is involved in macrophage phagocytosis through the competitive binding of SLAMF7 with miR-27b-3p. IMD induces the suppression of Dnm3os to inhibit macrophage phagocytosis and alleviate atherosclerosis in diabetes. • Atherosclerosis in diabetes is a leading cause of cardiovascular complications. • Intermedin inhibit macrophage phagocytosis in atherosclerosis. • Dnm3os/miR-27b-3p/SLAMF7 involved in macrophage phagocytosis. • IMD induces the suppression of Dnm3os to inhibit macrophage phagocytosis. [ABSTRACT FROM AUTHOR]

Background: Metastasis is the main cause of death in colorectal cancer (CRC). Circulating tumour cells (CTCs) are regarded as the precursor cells of metastasis. The CTCs, which underwent epithelial-mesenchymal transition (EMT), are associated with metastasis and responsible for poor prognosis. EMT cancer cells modulate endothelial permeability in the invasive front and facilitate cancer cell intravasation, resulting in CTCs-mediated distant metastasis. Exosomes derived from cancer cells are key mediators of cancer-host intercommunication. However, the mechanism by which EMT-tumour cells-derived exosomes modulate vascular permeability and promote CTCs generation has remained unclear. Methods: Exosomes isolation and purification were conducted by ultracentrifugation. Exosomal miRNA was identified by sequencing followed by quantitative PCR. In vitro co-culture assay experiments were conducted to evaluate the effect of exosomal miR-27b-3p on the permeability of blood vessel endothelium. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP) were performed to investigate the underlying mechanism by which miR-27b-3p is packaged into exosomes. A mouse model was established to determine the role of exosomal miR-27b-3p in blood vessel permeability modulation in vivo. Results: We found that EMT-CRC cells attenuate the blood vessel barrier by transferring miR-27b-3p to human umbilical vein endothelial cells (HUVECs) in exosomes. Mechanically, miR-27b-3p atteuated the expression of vascular endothelial cadherin (VE-Cad) and p120 at the post-transcriptional level by binding to 3'-untranslated region of VE-Cad and p120 directly. The packaging of miR-27b-3p into exosomes was induced by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which activated by STAT3. Clinically, miR-27b-3p up-regulated in CRC tissues. Plasma exosomal miR-27b-3p was positively correlated with malignant progression and CTC count in CRC patients. Our study reveals a novel mechanism by which EMT-CRC cells promote metastasis, increasing blood vessel permeability and facilitating the generation of CTCs. Conclusion: Exosomal miR-27b-3p secreted by EMT-CRC cells increases blood vessel permeability and facilitates the generation of CTCs. ExosomalmiR-27b-3p may become a promising biomarker for CRC metastasis. [ABSTRACT FROM AUTHOR]

The dysregulation of microRNAs (miRNAs) is a crucial molecular signature of disease development. The potential implication of miRNAs in neurofibromatosis type 1 (NF1) remains poorly investigated. The expression levels of miR-27a-3p, miR-27b-3p, and neurofibromin 1 (NF1) were detected by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. The functional roles of miR-27a-3p and miR-27b-3p in NF1 were explored by CCK8 (Cell Counting Kit-8), 5-ethynyl-2′-deoxyuridine (EdU), terminal deoxynucleoitidyl transferase dUTP nick-end labeling (TUNEL), and transwell assays. Luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation (RIP) assays were employed to study the probable target relationship between miRNA and messenger RNA (mRNA). MiR-27b-3p and miR-27a-3p were upregulated in dermal and plexiform human Schwann cells (HSC) from NF1 neurofibromas as well as cell lines of malignant peripheral nerve sheath tumors (MPNSTs). MiR-27a-3p/miR-27b-3p mimics promoted the proliferative, migratory, and invasive ability of dermal HSC and MPNST cell ST88-14, while inhibiting the apoptotic capacity. MiR-27a-3p/miR-27b-3p inhibitors elicited the opposite impacts on the above cellular behaviors in dermal HSC and ST88-14. Intriguingly, NF1 was revealed to be the target of both miR-27a-3p and miR-27b-3p, and was negatively modulated by them. MiR-27a-3p/miR-27b-3p upregulation suppressed the expression of NF1 in dermal HSC and ST88-14. Furthermore, NF1 depletion counterbalanced the functional alteration induced by miR-27a-3p/miR-27b-3p inhibition. Our study suggests that both miR-27b-3p and miR-27a-3p are involved in upstream molecular activity responsible for the depletion of NF1, representing promising targets for therapeutic application in NF1. [ABSTRACT FROM AUTHOR]

Lei Li, Guohua Lv, Bing Wang, Hong Ma Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaCorrespondence: Hong Ma Tel +86 731-85295124Email spinema@csu.edu.cnBackground: Chordoma, a rare bone tumor, occurs most commonly at the sacrococcygeal and skull base region. To date, chemotherapy is used to treat patients with advanced-stage chordoma. However, multidrug resistance (MDR) greatly hinders the effect of chemotherapy in chordoma. Here, we studied the correlation between KCNQ1OT1 and chemotherapy resistance.Methods: RT-PCR assay was used to examine KCNQ1OT1, miR-27b-3p, and ATF2 mRNA expression. CCK8 assay was exercised to detect IC50 values of cisplatin in chordoma cells. ATF2 protein expression was detected by Western blot.Results: KCNQ1OT1 was increased in chemotherapy-resistant patients and cisplatin-resistant cells, and downregulation of KCNQ1OT1 expression weakened MDR in chordoma. In addition, KCNQ1OT1 promoted MDR in chordoma by sponging miR-27b-3p and subsequently increasing ATF2 expression.Conclusion: KCNQ1OT1 is proved to be strikingly raised in the chemotherapy-resistant group and to promote MDR in chordoma. Our findings demonstrated the role of the KCNQ1OT1/miR-27b-3p/ATF2 axis in MDR of chordoma, which provides new insight into the molecular mechanism of chordoma MDR, and may determine the effect of therapy after receiving chemotherapy by detecting the expression of KCNQ1OT1 in serum.Keywords: KCNQ1OT1, MDR, miR-27b-3p, ATF2, chordoma

Background Understanding the mechanism of chondrocytes degeneration could provide a new potential therapeutic idea for rheumatoid arthritis (RA) treatment. MicroRNA-27b-3p (miR-27b-3p) has been shown to regulate a variety of cell behaviors in various cell types. However, the role of miR-27b-3p in RA remains unknown.Materials and methods Expression of miR-27b-3p and HIPK2 in cartilage tissues and chondrocytes was characterized using qRT-PCR and Western blot. MiR-27b-3p was overexpressed or suppressed in chondrocytes to observe the potential role of miR-27b-3p.Results We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells using qRT-PCR. Dual-luciferase reporter assay validated HIPK2 is a direct target of miR-27b-3p, confirmed by Western blot results. Pearson correlation presented that there was a significantly negative correlation between miR-27b-3p and HIPK2 mRNA. Overexpression of miR-27b-3p significantly reduced the expression of pro-apoptotic protein c-caspase3 and increased the expression of anti-apoptotic Bcl-2; however, downregulation of miR-27b-3p has a significant effect of inducing apoptosis. Furthermore, overexpression of miR-27b-3p combined with recombinant HIPK2 protein showed the inhibitory effect of miR-27b-3p was abolished by HIPK2.Conclusion We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells. Further in vitro studies demonstrated that miR-27b might inhibit chondrocyte apoptosis and thus attenuate RA development by directly inhibiting HIPK2 expression.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease and a common complication of SLE is lupus nephritis (LN) during which lupus autoantibodies and proinflammatory cytokines attack the kidney and cause renal dysfunction. The current treatments to LN are limited due to a poor understanding of the pathogenesis. Here, we studied the molecular mechanisms of LN by investigating the function of circELK4/miR-27b-3p axis. MRL/lpr mice and LPS-treated HK-2 cells were used as the mouse model and cell model of LN, respectively. Blood samples were collected from LN patients. qRT-PCR and western blot were used to measure expression levels of circELK4, miR-27b-3p, apoptosis-related proteins, cytokines, and STING/IRF-3/IFN-I signaling. ELISA was performed to examine levels of cytokines including IL-6 and TNF-α. H&E staining was used to examine kidney morphology. TUNEL staining and flow cytometry were used to determine cell apoptosis. Dual luciferase activity assay and RNA pull down were employed to validate the interactions of circELK4/miR-27b-3p and miR-27b-3p/STING. CircELK4 was elevated in LN mice, patients, and LPS-treated HK-2 cells. Knockdown of circELK4 attenuated renal injury in LN mice and LPS-induced HK-2 cell injury. CircELK4 directly bound to miR-27b-3p while miR-27b-3p targeted STING. Moreover, overexpression of circELK4 could partially reverse the effects of miR-27b-3p mimics on cell apoptosis and inflammation. Furthermore, circELK4/miR-27b-3p regulated renal cell damage via modulating STING/IRF3/IFN-I signaling. CircELK4 contributes to renal injury by promoting inflammation and cell apoptosis via acting as a miR-27b-3p sponge to modulate STING/IRF3/IFN-I signaling in LN. [ABSTRACT FROM AUTHOR]

Hypertrophic Scar (HS) is a complicated fibrotic disease. In addition, its pathogenesis is still to be further explored. Long non-coding RNAs (lncRNAs) have been proved to be participated in multiple diseases, including HS. However, the role of lncRNA TUG1 in HS remains unclear. The expression level of RNA and protein in cells were detected by q-PCR and western blot, respectively. MTT assay was performed to test the cell proliferation. Cell migration was detected by transwell assay. Cell apoptosis was measured by flow cytometry. Dual luciferase report assay and RNA pull down were used to verify the relationship between TUG1, miR-27b-3p and TAK1.TUG1 and TAK1 were upregulated in HS, while miR-27b-3p was downregulated. Knockdown of TUG1 significantly suppressed the proliferation and migration and induced the apoptosis of HS fibroblasts (HSF). In addition, silencing of TUG1 notably inhibited the extracellular matrix (ECM) biosynthesis in HSF. Overexpression of miR-27b-3p has the same effect on HS as that of TUG1 knockdown. Meanwhile, TUG1 could sponge miR-27b-3p, and TAK1 was the direct target of miR-27b-3p. Furthermore, knockdown of TUG1 significantly suppressed the fibrosis in HS via miR-27b-3p/TAK1/YAP/TAZ axis mediation. LncRNA TUG1 promotes the fibrosis in HS via sponging miR-27b-3p and then activates TAK1/YAP/TAZ pathway, which may serve as a potential target for treatment of HS. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a non-inflammatory degenerative disease, with progressive damages on the articular cartilages. In recent years, researchers have paid many efforts in the diagnostics and treatments of OA. However, no effective therapeutic method has been revealed to help inhibit the development of OA. Herein, we studied the roles and associations of PCAT-1 and miR-27-3p in the pathogenesis OA. Methods: OA articular cartilages and healthy articular cartilages were isolated for investigation. The chondrocytes were isolated from articular cartilage samples. QRT-PCR and western blotting were used for the detection of expression of genes and proteins. cell Titer 96® AQueous one proliferation kit was applied for detect cell viability of Chondrocytes transfected with negative control vector, pcDNA3.1 PCAT-1 plasmid or siRNA against PCAT-1. RNA pull-down assays and Luciferase reporter assay were used to confirm the connection. SPSS 17.0 was employed for statistical analysis. Results: We found that the expressions of PCAT-1 were up-regulated in OA chondrocytes compared with normal chondrocytes. si-PCAT-1 suppressed apoptotic OA chondrocytes. Over-expression of PCAT-1 enhanced the apoptosis of normal chondrocytes. In addition, the online database and luciferase assay confirmed that PCAT-1 could directly target miR-27b-3p. PCAT-1 could promote the apoptosis of OA and normal chondrocytes through binding with miR-27b-3p. Conclusions: Based on the comparisons and analysis, we could conclude that lncRNA PCAT-1 regulated the apoptosis of chondrocytes through sponging miR-27b-3p in OA. PCAT-1 has potential values to act as a new therapeutic target for OA patients. [ABSTRACT FROM AUTHOR]

Renal fibrosis is a pathologic change in chronic kidney disease (CKD). MicroRNAs (miRNAs) have been shown to play an important role in the development of renal fibrosis. However, the biological role of miR-27b-3p in renal fibrosis remains unclear. Thus, this study aimed to investigate the role of miR-27b-3p in the progression of renal fibrosis. In this study, HK-2 cells were stimulated with transforming growth factor (TGF)-β1 for mimicking fibrosis progression in vitro. The unilateral ureteric obstruction (UUO)-induced mice renal fibrosis in vivo was established as well. The results indicated that the overexpression of miR-27b-3p significantly inhibited epithelial-to-mesenchymal transition (EMT) in TGF-β1-stimulated HK-2 cells, as shown by the decreased expressions of α-SMA, collagen III, Fibronectin and Vimentin. In addition, overexpression of miR-27b-3p markedly decreased TGF-β1-induced apoptosis in HK-2 cells, as evidenced by the decreased levels of Fas, active caspase 8 and active caspase 3. Meanwhile, dual-luciferase assay showed that miR-27b-3p downregulated signal transducers and activators of transcription 1 (STAT1) expression through direct binding with the 3′-UTR of STAT1. Furthermore, overexpression of miR-27b-3p attenuated UUO-induced renal fibrosis via downregulation of STAT1, α-SMA and collagen III. In conclusion, miR-27b-3p overexpression could alleviate renal fibrosis via suppressing STAT1 in vivo and in vitro. Therefore, miR-27b-3p might be a promising therapeutic target for the treatment of renal fibrosis. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (LncRNAs) could regulate chemoresistance through sponging microRNAs (miRNAs) and sequestering RNA binding proteins. However, the mechanism of lncRNAs in rituximab resistance in diffuse large B-cell lymphoma (DLBCL) is largely unknown. Here, we investigated the functions and molecular mechanisms of lncRNA CHROMR in DLBCL tumorigenesis and chemoresistance. LncRNA CHROMR is highly expressed in DLBCL tissues and cells. We examined the oncogenic functions of lncRNA CHROMR in DLBCL by a panel of gain-or-loss-of-function assays and in vitro experiments. LncRNA CHROMR suppression promotes CD20 transcription in DLBCL cells and inhibits rituximab resistance. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assay reveal that lncRNA CHROMR sponges with miR-27b-3p to regulate mesenchymal-epithelial transition factor (MET) levels and Akt signaling in DLBCL cells. Targeting the lncRNA CHROMR/miR-27b-3p/MET axis reduces DLBCL tumorigenesis. Altogether, these findings provide a new regulatory model, lncRNA CHROMR/miR-27b-3p/MET, which can serve as a potential therapeutic target for DLBCL., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Epigenetics play a vital role in the initiation and development of cancers, including gastric cancer (GC). In the present study, we aimed to explore potential up- and downstream mechanisms of miR-27b-3p in GC. Methods: The expression level of miR-27b-3p in GC cells and tissues (n = 80) was measured by quantitative RT-PCR. The mimics, inhibitors, and negative controls of miR-27b-3p were transfected into cell lines to perform the gain and loss of function study. Cell proliferation, migration, and invasion assays were utilized to assess biological behaviors caused by miR-27b-3p in vitro. Common target genes were predicted using four biological software programs and used for gene functional enrichment analysis. GSPT1 was selected for target gene verification using dual luciferase assays and its expression level was detected by western blot. The MKN-45 cell line was treated with 5-aza-2′-deoxycytidine (5-Aza-dC) and the methylation level was measured by methylation-specific PCR (MSP). Results: miR-27b-3p was significantly downregulated in the GC cell lines and tissues compared with the normal group. The expression of miR-27b-3p was determined to be negatively associated with TNM stage and tumor size using statistical analysis. Overexpression of miR-27b-3p inhibited MKN-45 and SGC-7901 cell proliferation, invasion, and migration. Gene functional enrichment analysis indicated that the target genes were involved in several signaling pathways. Dual luciferase assays showed that miR-27b-3p combined with the 3′-untranslated region of GSPT1 mRNA. MSP demonstrated that miR-27b-3p promoter CpG island was hyper-methylated and 5-Aza-dC was able to partially reverse the methylation. Conclusions: Our study data indicated that miR-27b-3p is downregulated by aberrant DNA methylation in GC. In addition, miR-27b-3p suppresses GC cell proliferation, invasion, and migration via negative expression regulation of GSPT1, which could be a potential therapeutic target.

Background: An increasing number of studies demonstrate that long non-coding RNAs (lncRNAs) are regulators in cancer biology. Nevertheless, the expression and mechanism of LINC01089 in colorectal cancer (CRC) remain unclear. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was taken to investigate the expression levels of LINC01089 and miR-27b-3p in CRC tissues and cells. MTT method and transwell test were employed to assess the proliferation and invasion of CRC cells, respectively. Dual-luciferase activity reporter assay, RNA immunoprecipitation assay, Pearson's correlation analysis, and Western blot were performed to investigate the regulatory mechanism of LINC01089/miR-27b-3p/HOXA10 axis in CRC. Results: LINC01089 was down-regulated in CRC tissues and cell lines. LINC01089 overexpression impeded the proliferation and invasion of SW620 and LoVo cells, whereas LINC01089 knockdown increased the malignancy of SW480 and HT29 cells. Moreover, LINC01089 directly interacted with miR-27b-3p to repressed its expression and indirectly promoted the expression of HOXA10. Conclusion: LINC01089 impedes the proliferation and invasion of colorectal cancer cells by adsorbing miR-27b-3p and up-regulating the expression of HOXA10. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an industrial raw material widely used in water bottles, medical devices and food packaging, and is now ubiquitous in the environment. However, the effects of BPA on the toxicity of fish lymphocytes and the roles of microRNA (miRNA) in this process remain poorly understood. To explore the mechanism, we exposed carp spleen lymphocytes to BPA of 1, 5 and 10 nM for 24 h. The results showed that BPA induced carp lymphocyte apoptosis. BPA inhibited the expression of miR-27b-3p mRNA, thereby increasing the expression of cytochrome P450 1B1, increasing ROS levels, inhibiting SOD, CAT, GSH-PX activity, GSH content, promoting the accumulation of NOS and MDA. At the same time, BPA activated the mitochondrial apoptosis pathway, inhibited the expression of BCL-2, and promoted the expression of CytC, BAX, Caspase-9 and Caspase-3. Dual luciferase reporter system showed CYP1B1 is the target genes of miR-27b-3p and negatively regulated by it. Overexpression of miR-27b-3p partially reversed oxidative stress and apoptosis of carp spleen lymphocytes induced by BPA stimulation. Taken together, BPA exposure can target up regulate CYP1B1 expression by down regulating miR-27b-3p expression, thus causing oxidative stress and inducing apoptosis of carp spleen lymphocytes through mitochondrial pathway. Our study will provide theoretical basis for immunotoxicology mechanism research and environmental protection of BPA in fish. Image 1 • CYP1B1 is a target gene of miR-27b-3p in fish. • BPA exposure alters the expression of miR-27b-3p and CYP1B1 in carp lymphocytes, thereby inducing oxidative stress. • BPA exposure induces lymphocyte apoptosis through mitochondrial pathway. • Overexpress miR-27b-3p can partially reversed oxidative stress and apoptosis of lymphocytes induced by BPA stimulation. [ABSTRACT FROM AUTHOR]

Purpose: Long non-coding RNA P73 antisense RNA 1T (TP73-AS1) is a newly discovered lncRNA involved in the occurrence and development of several cancers. However, its role in lung cancer has not been well investigated yet. Methods: The expressions of TP73-AS1, microRNA-27b-3p (miR-27b-3p) and lysosomal-associated protein transmembrane-4 Beta (LAPTM4B) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Annexin V-FITC/PI and transwell assays, respectively. Tumor xenografts were applied to explore the role of TP73-AS1 in vivo. The target relationship was predicted by StarBase v.2.0 or TargetScan and confirmed by luciferase reporter assay. Pearson's coefficient assay was applied to assess the expression correlation between two groups. Protein expression levels were detected by Western blot. Results: We found that TP73-AS1 was strikingly up-regulated in lung cancer tissues and cells. TP73-AS1 depletion inhibited the growth and metastasis of lung cancer cells in vitro. Furthermore, TP73-AS1 could act as an endogenous sponge by directly binding miR-27b-3p, and a notable inverse correlation between them was also discovered. Importantly, knockdown of miR-27b-3p could reverse the inhibitory effects of TP73-AS1 depletion on the growth and metastasis of lung cancer cells. Besides, LAPTM4B was directly targeted by miR-27b-3p and could be co-regulated by TP73-AS1 and miR-27b-3p in lung cancer cells. Silencing TP73-AS1 hampered tumor growth by regulating miR-27b-3p/LAPTM4B axis in vivo. Conclusion: TP73-AS1 promoted the progression of lung cancer through regulating miR-27b-3p/LAPTM4B axis and it might be a potential target for diagnosis and treatment of lung cancer. [ABSTRACT FROM AUTHOR]

MiR-27b-3p has been reported to function as tumor suppressor in several tumors, including breast cancer and lung cancer. Recently, miR-27b-3p has been identified to be significantly down-regulated in esophageal cancer. However, the clinical significance and biological role of miR-27b-3p in esophageal squamous cell carcinoma (ESCC) still remain unclear. In this study, the expression levels of miR-27b-3p were significantly reduced in ESCC clinical tissues and ESCC cell lines (EC97069 and TE-1). Moreover, down-regulated expression of miR-27b-3p was associated with poor cell differentiation, TNM stage and lymph node metastasis. Specially, overexpression of miR-27b-3p significantly suppressed cell proliferation, migration and invasion in vitro using CCK-8 and transwell assays. Targetscan bioinformatics predictions and luciferase reporter assay confirmed that nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) was a direct target gene of miR-27b-3p. Nrf2 expression was significantly increased in ESCC tissues compared with adjacent tissues. Up-regulated expression of Nrf2 was correlated with TNM stage and lymph node metastasis. Functionally, knockdown of Nrf2 exhibited similar effects to overexpression of miR-27b-3p. Higher expression of ZO-1, E-cadherin and lower expression of N-cadherin, Vimentin and Claudin-1 were observed after miR-27b-3p overexpression of Nrf2 knockdown. Rescue experiments proved that miR-27b-3p suppressed cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) via suppression of Nrf2. Taken together, the newly identified miR-27b-3p/Nrf2 axis might represent a new candidate therapeutic target for ESCC treatment. [ABSTRACT FROM AUTHOR]

Background: Understanding the mechanism of chondrocytes degeneration could provide a new potential therapeutic idea for rheumatoid arthritis (RA) treatment. MicroRNA-27b-3p (miR-27b-3p) has been shown to regulate a variety of cell behaviors in various cell types. However, the role of miR-27b-3p in RA remains unknown. Materials and methods: Expression of miR-27b-3p and HIPK2 in cartilage tissues and chondrocytes was characterized using qRT-PCR and Western blot. MiR-27b-3p was overexpressed or suppressed in chondrocytes to observe the potential role of miR-27b-3p. Results: We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells using qRT-PCR. Dual-luciferase reporter assay validated HIPK2 is a direct target of miR-27b-3p, confirmed by Western blot results. Pearson correlation presented that there was a significantly negative correlation between miR-27b-3p and HIPK2 mRNA. Overexpression of miR-27b-3p significantly reduced the expression of pro-apoptotic protein c-caspase3 and increased the expression of anti-apoptotic Bcl-2; however, downregulation of miR-27b-3p has a significant effect of inducing apoptosis. Furthermore, overexpression of miR-27b-3p combined with recombinant HIPK2 protein showed the inhibitory effect of miR-27b-3p was abolished by HIPK2. Conclusion: We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells. Further in vitro studies demonstrated that miR-27b might inhibit chondrocyte apoptosis and thus attenuate RA development by directly inhibiting HIPK2 expression. [ABSTRACT FROM AUTHOR]

Stress-induced immunosuppression (SIIS) is one of the common problems in intensive poultry production, which often reduces the prevention and control effects of various vaccines, including infectious bursal disease virus (IBDV) vaccine, and brings enormous economic losses to the poultry industry. However, the molecular mechanisms of SIIS inhibiting immune response to IBDV vaccine remain unclear. In this study, suppressor of cytokine signaling 3 ( SOCS3 ) gene was selected and stress-induced immunosuppressed chickens were simulated using dexamethasone (Dex). Quantitative real-time PCR (qRT-PCR) was conducted to analyze its expression characteristics and game relationships between SOCS3 gene and miR-27b-3p (it could target SOCS3 gene) in the process of SIIS inhibiting immune response to IBDV vaccine in chicken, and the potential application value of circulating miR-27b-3p as a biomarker was also identified. The results showed that SOCS3 gene and miR-27b-3p were significantly differentially expressed in the candidate tissues during SIIS inhibiting the immune response to IBDV (P < 0.05), respectively, which were key factors involved in the process. Moreover, miR-27b-3p and SOCS3 gene showed game regulation relationships in several tissues during the process, so the miR-27b-3p/SOCS3 regulatory network was one of the key mechanisms of SOCS3 gene participating in the process. Circulating miR-27b-3p was differentially expressed in serum at 10 time points (1, 2, 3, 4, 5, 7, 14, 21, 28, and 35 days postimmunization (dpi)) in the process (P < 0.05), showing that circulating miR-27b-3p was a valid candidate target as a molecular marker for detecting SIIS inhibiting the IBDV immune response. This study can provide references for further studying molecular mechanisms of stress affecting immune response. [ABSTRACT FROM AUTHOR]

Objective: Long-term dysregulation of energy balance is the key component of the obesity epidemic. Given the harm of central obesity and the discovery that beige cells appear within white adipose tissue (WAT), enhancing the energy-expending or “browning” ability of visceral adipose tissue (VAT) has become of therapeutic interest. In this study, we focused on the regulating role of microRNA (miRNA)-27b-3p in mice epididymal white adipose tissue (eWAT) browning.Methods: High-fat diet (HFD) induced obese mice model was constructed. Expression of miR-27b-3p and Ucp1 in eWAT was measured during the course of HFD. Through tail vein injection of antimiR-27b-3p, miR-27b-3p expression was inhibited to analyze the potential role of miR-27b-3p in fat browning and metabolism.Results: miR-27b-3p was predominantly expressed in eWAT and browning ability of eWAT in HFD induced obese mice was impaired. Inhibition of miR-27b-3p enhanced browning capacity of eWAT in mice fed an HFD and led to weight loss and insulin sensitivity improvement.Conclusions: High expression of miR-27b-3p in eWAT inhibits browning ability and leads to visceral fat accumulation. It is suggested miR-27b-3p may become a potential therapeutic option for visceral obesity and its associated diseases.

Background: To investigate the roles of extracellular vesicles (EVs) secreted from bone marrow mesenchymal stem cells (BMSCs) and miR-27 (highly expressed in BMSC EVs) in hepatic ischemia‒ reperfusion injury (HIRI)., Approaches and Results: We constructed a HIRI mouse model and pretreated it with an injection of agomir- miR-27-3p , agomir-NC, BMSC-EVs or control normal PBS into the abdominal cavity. Compared with the HIRI group, HIRI mice preinjected with BMSC-EVs had significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated liver necrosis (P<0.05). However, compared with HIRI+NC mice, HIRI+ miR-27b mice had significantly increased ALT and AST levels, aggravated liver necrosis, and increased apoptosis-related protein expression (P<0.05). The proliferation and apoptosis of AML-12 cells transfected with miR-27 were significantly higher than the proliferation and apoptosis of AML-12 cells in the mimic NC group (P<0.01) after hypoxia induction. SMAD4 was proven to be a miR-27 target gene. Furthermore, compared to HIRI+NC mice, HIRI+ miR-27 mice displayed extremely reduced SMAD4 expression and increased levels of wnt1, β-catenin, c-Myc, and Cyclin D1., Conclusion: Our findings reveal the role and mechanism of miR-27 in HIRI and provide novel insights for the prevention and treatment of HIRI; for example, EVs derived from BMSCs transfected with antimiR- 27 might demonstrate better protection against HIRI., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

microRNAs play an important role in the growth and development of chicken embryos, including the regulation of skeletal muscle genesis, myoblast proliferation, differentiation, and apoptosis. Our previous RNA-seq studies showed that microRNA-27b-3p (miR-27b-3p) might play an important role in regulating the proliferation and differentiation of chicken primary myoblasts (CPMs). However, the mechanism of miR-27b-3p regulating the proliferation and differentiation of CPMs is still unclear. In this study, the results showed that miR-27b-3p significantly promoted the proliferation of CPMs and inhibited the differentiation of CPMs. Then, myostatin (MSTN) was confirmed to be the target gene of miR-27b-3p by double luciferase reporter assay, RT-qPCR, and Western blot. By overexpressing and interfering with MSTN expression in CPMs, the results showed that overexpression of MSTN significantly inhibited the proliferation and differentiation of CPMs. In contrast, interference of MSTN expression had the opposite effect. This study showed that miR-27b-3p could promote the proliferation of CPMs by targeting MSTN. Interestingly, both miR-27b-3p and MSTN can inhibit the differentiation of CPMs. These results provide a theoretical basis for further understanding the function of miR-27b-3p in chicken and revealing its regulation mechanism on chicken muscle growth.

Background: Acute kidney injury (AKI) shows several kinds of disorders, which acutely harm the kidney. However, the current medical methods have limited therapeutic effects. The present study aimed to find out the molecular mechanism of AKI pathogenesis, which may provide new insights for future therapy. Methods: Bioinformatic analysis was conducted using the R language (AT&T BellLaboratories, University of Auckland, New Zealand) to acquire the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in AKI. The expression levels of RNAs and related proteins in tissues and cells were detected by quantitative real‐time PCR (qRT‐PCR) and western blot. Dual‐luciferase reporter gene assays were performed to verify the target relationship between microRNA (miRNA) and lncRNA as well as miRNA and mRNA. Flow cytometry and tunnel assay were used to detect the cell apoptotic rate in AKI. Results: LINC00520, miR‐27b‐3p, and OSMR form an axis to regulate AKI. Knockdown of LINC00520 reduced acute renal injury both in vitro and in vivo. LINC00520 activated the PI3K/AKT pathway to aggravate renal ischemia/reperfusion injury, while upregulation of miR‐27b‐3p or downregulation of OSMR could accelerate the recovery of AKI. Conclusion: Overexpression of LINC00520 contributes to the aggravation of AKI by targeting miR‐27b‐3p/ OSMR. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a kind of microvascular complications of diabetes. Long noncoding RNAs (lnRNAs) can participate in the development of various diseases, including DN. However, the function of lncRNA NEAT1 is unclear. In our present study, we reported that NEAT1 was significantly increased in streptozotocin‐induced DN rat models and high‐glucose‐induced mice mesangial cells. We observed that knockdown of NEAT1 greatly inhibited renal injury of DN rats. Meanwhile, downregulation of NEAT1‐modulated extracellular matrix (ECM) proteins (ASK1, fibronectin, and TGF‐β1) expression and epithelial–mesenchymal transition (EMT) proteins (E‐cadherin and N‐cadherin) in vitro. Previously, miR‐27b‐3p has been reported to be involved in diabetes. Here, miR‐27b‐3p was decreased in DN rats and high‐glucose‐induced mice mesangial cells. The direct correlation between NEAT1 and miR‐27b‐3p was validated using the dual‐luciferase reporter assay and RNA immunoprecipitation experiments. In addition, zinc finger E‐box binding homeobox 1 (ZEB1), which has been identified in the process of EMT clearly contributes to EMT progression. ZEB1 was predicted as a target of miR‐27b‐3p and overexpression of miR‐27b‐3p dramatically repressed ZEB1 expression. Therefore, our data implied the potential role of NEAT1 in the fibrogenesis and EMT in DN via targeting miR‐27b‐3p and ZEB1. [ABSTRACT FROM AUTHOR]

Long noncoding RNA KCNQ1OT1 participates in the regulation of imprinted genes within the kcnq1 domain. But its roles in carcinogenesis and metastasis remain largely elusive. Herein, we evaluated its potential in non‐small‐cell lung cancer (NSCLC) progression. We demonstrated that the KCNQ1OT1 level was upregulated in NSCLC tissues and cell lines. High KCNQ1OT1 level correlated with poor overall and progression‐free survival in NSCLC patients. KCNQ1OT1 facilitated proliferation, migration, and invasion in H460 cells. Furthermore, knockdown of KCNQ1OT1 reduced the expression of HSP90AA1. KCNQ1OT1 presented a positive correlation with HSP90AA1 which predicted the tumor progression in NSCLC from The Cancer Genome Atlas database. Intriguingly, KCNQ1OT1 modulated HSP90AA1 expression by sponging miR‐27b‐3p. MiR‐27b‐3p counteracted the effect of KCNQ1OT1 on HSP90AA1 expression, H460 cell migration, and invasion. These data revealed a role for KCNQ1OT1 as an oncogene through miR‐27b‐3p/HSP90AA1 axis during NSCLC progression. Long noncoding RNA KCNQ1OT1 promotes non‐small‐cell lung cancer progression. KCNQ1OT1 modulates HSP90AA1 expression by sponging miR‐27b‐3p. [ABSTRACT FROM AUTHOR]

Oral lichen planus (OLP) is considered a precancerous lesion with no known cure. Recent studies reported that abnormal regulation of apoptosis was involved in the pathogenesis of OLP. Next generation sequencing was used to screen the candidate microRNAs and genes in biopsies from patients with OLP and healthy mucosa. Human oral keratinocytes were transfected into the related oligonucleotides of miR‐27b‐3p/cyclophilin D and their control groups. Apoptosis was detected by TdT‐mediated dUTP nick end labelling and flow cytometry. The levels of mRNA and protein were detected by quantitative PCR, Western blots, and enzyme‐linked immunosorbent assays, respectively. Luciferase assays were performed to detect the luciferase activities of miR‐27b‐3p and cyclophilin D. Here, we showed that basal epithelium apoptosis was reduced and the miR‐27b‐3p levels were decreased in clinical OLP samples. We also found that down‐regulation of miR‐27b‐3p inhibited epithelial keratinocyte apoptosis by up‐regulating cyclophilin D expression. Moreover, cyclophilin D increased the protein stability of Bcl2 through direct binding, and Bcl2 suppressed caspase9/3 activation and cytochrome C release. Taken together, these data showed that miR‐27b‐3p regulated keratinocyte apoptosis through cyclophilin D/Bcl2 signalling, suggesting the miR‐27b‐3p regulated the pathogenesis of OLP. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) has a significant impact on human health. The aim of this study was to explore the role of long non-coding RNA DLX6-AS1 in the proliferation, migration, and invasion of NSCLC cells. Methods: The expression of DLX6-AS1 in NSCLC tumor tissues and cell lines was examined by qRT-PCR. The effects of DLX6-AS1 knockdown on cell proliferation, migration, and invasion were assessed by Cell Counting Kit-8, wound healing, and transwell assays, respectively. Bioinformatics analyses, luciferase reporter assays, and RNA pull-down assays were employed to examine the mechanism by which DLX6-AS1 exerted its oncogenesis effects in NSCLC. The anti-tumor effect of silencing DLX6-AS1 in vivo was also evaluated. Results: DLX6-AS1 was over-expressed in NSCLC tumor tissues and cell lines and its level of expression was found to be associated with tumor size and advanced clinical stage in patients with NSCLC. Downregulation of DLX6-AS1 inhibited cell proliferation, cell clone formation, migration, and invasion of NSCLC cells. DLX6-AS1 was found to interact with miR-27b-3p/GSPT1. DLX6-AS1 expression was negatively correlated with miR-27b-3p expression, but positively correlated with GSPT1 expression in NSCLC samples. DLX6-AS1 knockdown also effectively suppressed tumor growth in an in vivo xenograft model. Conclusion: DLX6-AS1 regulated NSCLC progression by targeting the miR-27b-3p/GSPT1 axis, which may provide novel insights for NSCLC prognosis and therapy. [ABSTRACT FROM AUTHOR]