LncRNA LINC00968 accelerates the proliferation and fibrosis of diabetic nephropathy by epigenetically repressing p21 via recruiting EZH2.

Emerging evidence have indicated the vital roles of long noncoding RNAs (lncRNAs) in the pathophysiological process of diabetic nephropathy. However, the deepgoing mechanism that lncRNAs regulate the diabetic nephropathy pathogenesis is still ambiguous. In present study, we found that lncRNA LINC00968 expression was high-expressed in the diabetic db/db mouse tissue and high-glucose induced mesangial cells. Functional experiments indicated that LINC00968 silencing by siRNAs significantly inhibited the proliferation and cycle progression, and decreased the extracellular matrix (ECM) proteins (fibronectin, collagen IV) expression in the high glucose induced of mesangial cells. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assay revealed that LINC00968 recruit EZH2 to the promoter of p21 to inhibit its expression. In summary, our results support the conclusion that lncRNA LINC00968 accelerates the proliferation and fibrosis of mesangial cells by epigenetically repressing p21 via recruiting EZH2, providing a novel insight for the diabetic nephropathy pathogenesis.

CircSHOC2 Knockdown Alleviates High Glucose-Induced Vascular Endothelial Cell Pyroptosis via Targeting miR-145/FOXO1 Axis In Vitro Condition.

Emerging evidence indicates that pyroptosis participates in the pathogenic process of vascular endothelial cells in cardiovascular system complications of diabetes. The roles of circular RNAs (circRNAs) in high glucose (HG)-induced vascular endothelial cells are still unclear. Here, our research investigated the function and mechanism of circRNA circSHOC2 in pyroptosis of vascular endothelial cells. Results indicated that circSHOC2 was up-regulated in HG-induced human umbilical vein endothelial cells (HUVECs). Functionally, cellular assays indicated that circSHOC2 silencing repressed HG-induced HUVECs pyroptosis. Moreover, circSHOC2 targeted miR-145 through miRNA sponge, and FOXO1 functioned as downstream target of miR-145. In conclusion, these findings suggested the potential roles of circSHOC2 on HG-induced vascular endothelial cells in vitro condition, providing new insights for cardiovascular system complications of diabetes.

N6-methyladenosine (m6A) writer METTL3 accelerates the apoptosis of vascular endothelial cells in high glucose.

Recent studies have shown that N6-methyladenosine (m6A) methylation, one of the most prevalent epigenetic modifications, is involved in diabetes mellitus. However, whether m6A regulates diabetic vascular endothelium injury is still elusive. Present research aimed to investigate the regulation and mechanism of m6A on vascular endothelium injury. Upregulation of METTL3 was observed in the high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs), following with the upregulation of m6A methylation level. Functionally, METTL3 silencing repressed the apoptosis and recovered the proliferation of HUVECs disposed by HG. Moreover, HG exposure upregulated the expression of suppressor of cytokine signaling3 (SOCS3). Mechanistically, METTL3 targeted the m6A site on SOCS3 mRNA, which positively regulated the mRNA stability of SOCS3. In conclusion, METTL3 silencing attenuated the HG-induced vascular endothelium cells injury via promoting SOCS3 stability. In conclusion, this research expands the understanding of m6A on vasculopathy in diabetes mellitus and provides a potential strategy for the protection of vascular endothelial injury.

miR-194 suppresses high glucose-induced non-small cell lung cancer cell progression by targeting NFAT5.

BACKGROUND: Diabetes mellitus (DM) is linked to an increased risk of lung cancer; however, the exact molecular basis is unclear. METHODS: We used a microarray method and found a group of microRNAs differently expressed in lung cancer cells at high or low glucose treatment. RESULTS: Among these, miR-194 changed significantly, which indicated further analysis. miR-194 was significantly downregulated in non-small cell lung cancer (NSCLC) cells cultured in high glucose (HG) medium and clinical NSCLC tissues with DM. The introduction of miR-194 significantly suppressed the proliferation, migration, and invasion of lung cancer cells induced by HG, suggesting that miR-194 may be a suppressor during HG-induced NSCLC progression. Further analysis indicated that NFAT5 was a direct target gene of miR-194, evidenced by the direct binding of miR-194 with the 3'untranslated region of NFAT5. MiR-194 could decrease the expression of NFAT5 at both messenger RNA and protein levels, while overexpression of NFAT5 reversed the decreased proliferation, migration, and invasion ability mediated by miR-194 in lung cancer cells. CONCLUSION: Our findings provide new insight into the mechanism of NSCLC progression. Therapeutically, miR-194 may serve as a potential target for the treatment of lung cancer patients with DM.

Long noncoding RNA GAS5 impairs the proliferation and invasion of endometrial carcinoma induced by high glucose via targeting miR-222-3p/p27.

Long noncoding RNAs (lncRNAs) have been identified to be critical functional regulator in the human tumors, while the deepgoing mechanism by which lncRNAs modulates the endometrial carcinoma is still elusive. In this work, we found that lncRNA GAS5 was under-expressed in the endometrial carcinoma tissue specimens, especially these samples with type 2 diabetes mellitus. Besides, the aberrant under-expression of GAS5 was correlated with the advanced tumor stage as well as poor prognosis outcome. In cellular experiments, GAS5 was decreased in the cells exposed to the high glucose. Enforced GAS5 expression repressed the tumor phenotype of endometrial carcinoma cells, including proliferation and invasion. Molecular mechanism study further demonstrated that GAS5 functioned as a sponge for miR-222-3p, abrogating its ability of inhibiting p27 protein expression. In conclusion, these results confirmed the vital regulation of GAS5/miR-222-3p/p27 axis in the endometrial carcinoma tumorigenesis.

Association of the Transcription Factor 7 Like 2 (TCF7L2) Polymorphism With Diabetic Nephropathy Risk: A Meta-Analysis.

It is assumed that genetic factors may participate in the development of diabetic nephropathy (DN). The association between TCF7L2 gene polymorphism and DN risk is still unclear. To evaluate the relationship, we performed this meta-analysis. Eligible relevant studies were searched and selected from PubMed, Embase, and ISI Web of Science. Summary effect estimates were derived using a random effects model, with attention to study quality and publication bias. Ethnical approval was not necessary, because this meta-analysis was based on published articles, and did not involve patient consent. A total of 7 studies were identified. Analysis of all studies indicated significant association between TCF7L2 gene polymorphism and DN risk (odds ratio [OR] = 1.31, 95% confidence interval (CI) = 1.10-1.56, Pheterogeneity < 0.00001, P = 0.002). Subgroup analysis showed similar results in Asian (OR = 1.33, 95% CI = 1.10-1.62, Pheterogeneity = 0.03, P = 0.004), in Caucasian (OR = 2.27, 95% CI = 1.78-2.90, Pheterogeneity = 0.17, P < 0.00001), in rs7903146 mutation (OR = 1.61, 95% CI = 1.25-2.07, Pheterogeneity < 0.00001, P = 0.0002), However, no association was observed in Negroid (OR = 1.10, 95% CI = 0.90-1.35, Pheterogeneity < 00001, P = 0.36). Our results suggest that TCF7L2 gene polymorphism may contribute to the risk of DN. However, more studies should be launched in the future.