7077

TIMP2

Carcinogenesis is a complex process during which cells undergo genetic and epigenetic alterations. MicroRNAs control gene expression by negatively regulating protein-coding mRNAs. Several reports demonstrated that miR-106a is up-regulated in gastric and colorectal cancers and promotes tumor progression. In contrast, in glioma miR-106a plays the role of a tumor suppressor gene rather than an oncogene. Here we demonstrate that a high level of miR-106a expression is present in pancreatic cancer. Furthermore, our investigation shows that miR-106a has an oncogenic role in pancreatic tumorigenesis by promoting cancer cell proliferation, epithelial-mesenchymal transition and invasion by targeting tissue inhibitors of metalloproteinase 2 (TIMP-2). MiR-106a could be a critical therapeutic target in pancreatic cancer.CI - Copyright (c) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease characterized by hyperandrogenism, irregular menses, and polycystic ovaries. Several long non-coding RNAs (lncRNAs) are aberrantly expressed in PCOS patients; however, little is known about the effects of the lncRNA-low expression in tumor (lncRNA-LET) on PCOS. We aimed to explore the effects of lncRNA-LET on human granulosa-like tumor cell line, KGN. METHODS: expression of lncRNA-LET in normal IOSE80 cells and granulosa cells was determined by qRT-PCR. KGN cell viability, apoptosis and migration were measured by trypan blue exclusion method, flow cytometry assay and wound healing assay, respectively. TGF-beta1 was used to induce epithelial-mesenchymal transition (EMT) process. LncRNA-LET expression and mRNA expressions of TIMP2 and EMT-related proteins were measured by qRT-PCR. Western blot analysis was used to measure the protein expression of apoptosis-related proteins, EMT-related proteins, TIMP2, and the proteins in the Wnt/beta-catenin and Notch signaling pathways. RESULTS: lncRNA-LET was down-regulated in KGN cells, and its overexpression inhibited cell viability and migration, and promoted apoptosis in KGN cells. Overexpression of lncRNA-LET increased the expression of E-cadherin and decreased the expressions of N-cadherin and vimentin in KGN cells. These effects of lncRNA-LET on KGN cells were reversed by TIMP2 suppression. Overexpression of TIMP2 inhibited cell viability, migration and EMT process, and increased apoptosis by activating the Wnt/beta-catenin and Notch pathways. CONCLUSION: Overexpression of lncRNA-LET inhibits cell viability, migration and EMT process, and increases apoptosis in KGN cells by up-regulating the expression of TIMP2 and activating the Wnt/beta-catenin and notch signaling pathways.CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved.

MicroRNAs (miRNAs), a group of short (~20 nt) noncoding RNAs, play critical roles in the development and progression of ovarian cancer (OC). The role of miR616, a recently identified cancer-associated miRNA, has never been examined in OC before. The present study demonstrated that the level of miR616 was increased in OC tissues. A high miR616 level was associated with poor tumor differentiation and advanced tumor-node-metastasis (TNM) stage. Survival analysis revealed that an elevated level of miR616 was associated with poor prognosis of OC patients as demonstrated by decreased overall survival (OS) and diseasefree survival (DFS). Overexpression of miR616 promoted the migration, invasion as well as epithelial-mesenchymal transition (EMT) of A2780 cells. Knockdown of miR616 inhibited these biological functions. Immunohistochemical (IHC) staining revealed that OC tissues with high miR616 levels exhibited a significantly decreased level of Ecadherin and an increased level of Ncadherin. Furthermore, tissue inhibitor of metalloproteinases 2 (TIMP2) was confirmed to be a direct downstream target of miR616. Inhibition of TIMP2 expression was required for the promoting effects of miR616 on the metastasis and EMT of OC cells. Collectively, this study revealed that miR616 promoted the progression of OC by enhancing cell migration, invasion and EMT.