407001

MIR218-2

A major reason for oxaliplatin chemoresistance in colorectal cancer is the acquisition of epithelial-mesenchymal transition (EMT) in cancer cells. The long noncoding RNA (lncRNA), MALAT1, is a highly conserved nuclear ncRNA and a key regulator of metastasis development in several cancers. However, its role in oxaliplatin-induced metastasis and chemoresistance is not well known. In this study, we aim to investigate the prognostic and therapeutic role of lncRNA MALAT1 in colorectal cancer patients receiving oxaliplatin-based therapy and further explore the potential transcriptional regulation through interaction with EZH2 based on the established HT29 oxaliplatin-resistant cells. Our results showed that high MALAT1 expression was associated with reduced patient survival and poor response to oxaliplatin-based chemotherapy in advanced colorectal cancer patients. Oxaliplatin-resistant colorectal cancer cells exhibited high MALAT1 expression and EMT. LncRNA MALAT1 knockdown enhances E-cadherin expression and inhibits oxaliplatin-induced EMT in colorectal cancer cells. EZH2 is highly expressed and associated with the 3' end region of lncRNA MALAT1 in colorectal cancer, and this association suppressed the expression of E-cadherin. Furthermore, targeted inhibition of MALAT1 or EZH2 reversed EMT and chemoresistance induced by oxaliplatin. Finally, the interaction between lncRNA MALAT1 and miR-218 was observed, which further indicated its prognostic value in patients who received standard FOLFOX (oxaliplatin combine with 5-fluorouracil and leucovorin) treatment. In conclusion, this study illuminates the prognostic role of lncRNA MALAT1 in colorectal cancer patients receiving oxaliplatin-based treatment and further demonstrates how lncRNA MALAT1 confers a chemoresistant function in colorectal cancer. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for colorectal cancer patients. Mol cancer Ther; 16(4); 739-51. (c)2017 AACR.CI - (c)2017 American Association for cancer Research.

BACKGROUND: Previous studies indicated that miR-218 was deregulated in gastric cancer patients and correlated with tumor invasion and prognosis. The aim of this study was to clarify the effect of miR-218 on the malignant behavior of gastric cancer and its role in regulating Bmi-1/Akt signaling pathway. MATERIALS AND METHODS: We used miR-218 mimic to transfect gastric cancer cell lines AGS and SGC-7901, and the overexpression efficiency was validated using qRT-PCR assay. MTT assay and Transwell chamber system were performed to detect the effect of miR-218 on cell proliferation, invasion and migration on gastric cancer. Western blot and qRT-PCR assay was used to test the role of miR-218 in regulating Bmi-1/Akt signaling pathway. RESULTS: As shown in our research, ectopic expression of miR-218 in gastric cancer cells inhibits the proliferation, invasion and migration of gastric cancer cells. In addition, miR-218 re-expression inhibits the expression of Bmi-1 and its downstream target p-Akt(473), as well as MMPs and EMT process. CONCLUSIONS: miR-218 inhibits the proliferation, invasion and migration of gastric cancer cells through modulating EMT process and the expression of MMPs via Bmi-1/Akt signaling pathway.CI - Copyright (c) 2018. Published by Elsevier GmbH.