MicroRNA-141 inhibits proliferation of gastric cardia adenocarcinoma by targeting MACC1

MicroRNA-141通过靶向MACC1抑制胃贲门腺癌的增殖

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Abstract

INTRODUCTION: Abnormal expression of microRNAs (miRNAs) contributes to cancer development through regulating proliferation, apoptosis and drug resistance in cancer cells. The present study was designed to explore the effect and mechanism of miR-141 on gastric cardia adenocarcinoma (GCA). MATERIAL AND METHODS: Forty-one paired GCA tissues and adjacent normal tissues were obtained from GCA patients never treated by chemotherapy or radiotherapy. QRT-PCR was used to detect the expression level of miR-141 in GCA. Effects of miR-141 on cell proliferation and apoptosis were detected in vitro. Western blot analysis was used to determine the downstream targets of miR-141. RESULTS: In the present study, our data showed that miR-141 was significantly decreased and correlated with advanced TNM stage and lymph node metastases in GCA. In addition, we found that miR-141 could inhibit cell proliferation and induce cell apoptosis in AGS cells. Moreover, MACC1 was predicted as a possible target of miR-141. The luciferase reporter assay proved that miR-141 could suppress MACC1 directly by binding to its 3'-UTR. Further studies showed that miR-141 influenced the MEK/ERK and p38 MAPK signaling pathways. CONCLUSIONS: Our findings demonstrated that miR-141 expression was associated with GCA progression. MACC1, working as one possible target of miR-141, may contribute to the process. MiR-141 is expected to be a potential therapeutic target for the treatment of GCA patients.

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