IL6R inhibits viability and apoptosis of pancreatic beta-cells in type 2 diabetes mellitus via regulation by miR-22 of the JAK/STAT signaling pathway.

BACKGROUND AND AIM: Type 2 diabetes mellitus (T2DM) is a common disease of harming to people's health. MicroRNAs have recently been considered as key regulators of many biological processes, such as cell proliferation, migration and apoptosis. However, the effect of miR-22 expression by targeting IL6 receptor (IL6R) in T2DM and potential molecular mechanism involved remains to be elucidated. The present study aimed to explore the regulatory mechanism of miR-22 by targeting IL6R in pancreatic beta-cells viability and apoptosis of T2DM. METHODS: The expressions of miR-22, IL6R and apolipoprotein (apoA1, apoB and apoE) were examined by reverse transcription-quantitative PCR (qRT-PCR). Pancreatic beta-cells were transiently transfected with a miR-22 mimic or si-IL6R plasmid which validated with qRT-PCR to analyze the expression of miR-22 or IL6R. Cell viability, apoptosis and protein expression levels were determined by CCK-8, flow cytometry and Western blotting, respectively. RESULTS: The proportion of INS-1E cell apoptosis was increased in islets of diabetic rats. Furthermore, miR-22 was downregulated and IL6R was upregulated in both diabetic serum and glucose-induced INS-1E cells. miR-22 overexpression or IL6R inhibition significantly strengthened cell viability and reduced the expression of apoptosis-related proteins to suppress cell apoptosis. IL6R was demonstrated as a target gene of miR-22 which could negatively regulate IL6R expression. Moreover, phosphorylation of JAK/STAT signaling pathway was activated by miR-22 overexpression or IL6R inhibition to strengthen the viability and suppress apoptosis of INS-1E cells. CONCLUSION: This study indicated that miR-22 strengthened the viability and suppressed apoptosis of INS-1E cells, partly by down-regulation of IL6R through the activation of JAK/STAT signaling pathway.

DNA copy number gain-mediated lncRNA LINC01061 upregulation predicts poor prognosis and promotes papillary thyroid cancer progression.

Several DNA copy number amplifications (CNAs) have been reported in papillary thyroid cancer (PTC). However, the functional role of CNAs in PTC remains very unclear. And whether there is a correlation between long noncoding RNA (lncRNA) and CNA requires to be explored. Here, we identified a novel lncRNA LINC01061. The genomic copy number of LINC01061 is amplified, which leads to its elevated expression level in PTC tissues. Moreover, increased level of LINC01061 was correlated with aggressive clinicopathological characteristics. Functional study indicated that LINC01061 silence significantly inhibited the proliferation, cell-cycle and invasion of PTC cells in vitro and tumor growth in vivo. Mechanistically, we showed that LINC01061 interacted with miR-4316 to promote E2F6 expression. The expression of miR-4316 was downregulated in PTC tissues while that of E2F6 was upregulated. Through rescue assay, we demonstrated that LINC01061 promoted PTC cell proliferation, cell-cycle progression and invasion by regulating miR-4316/E2F6 signaling pathway. In conclusion, our research indicated that LINC01061 might be a target for PTC therapy.