J Cancer 2020; 11(21):6277-6285. doi:10.7150/jca.44037

Research Paper

MiR-137 promotes anoikis through modulating the AKT signaling pathways in Pancreatic Cancer

Lin Li1,2,3,4*, Zhiwei He1,2,3*, Changhao Zhu1,2,3,4*, Shiyu Chen1,2,3,4, Zhehao Yang1,2,3, Jing Xu1,2,3, Ningrui Bi1,2,3, Chao Yu1,2,3✉, Chengyi Sun1,2,3✉

1. Guizhou Medical University, Guiyang, China.
2. Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
3. Key Laboratory of Hepatobiliary and Pancreatic Surgery, Guiyang, China.
4. College of Basic Medicine, Guizhou Medical University, Guiyang, China.
*These authors contributed equally to this study.

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Citation:
Li L, He Z, Zhu C, Chen S, Yang Z, Xu J, Bi N, Yu C, Sun C. MiR-137 promotes anoikis through modulating the AKT signaling pathways in Pancreatic Cancer. J Cancer 2020; 11(21):6277-6285. doi:10.7150/jca.44037. Available from http://www.jcancer.org/v11p6277.htm

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Abstract

Anoikis resistance is a fundamental feature of the survival of metastatic cancer cells during cancer progression. However, the mechanisms underlying anoikis resistance in pancreatic cancer (PC) are still unclear. MicroRNA-137 (miR-137) is a tumor suppressor that inhibits the proliferation and invasion of cancer cells through targeting multiple oncogenes. However, the effects and molecular mechanism of miR-137 on anoikis of PC are still unclear. Here we demonstrated that miR-137 was downregulated after the induction of anoikis model in time dependent. Function assays revealed that miR-137 promoted the pancreatic cancer cells anoikis in vitro and vivo. According to bioinformation analysis of clinical databases, we predicted that paxillin (PXN) was a target of miR-137. Further, TCGA analysis revealed that PXN was closely associated with the development of PC. Through loss-of-function studies, we demonstrated that PXN was a functional target of miR-137 on anoikis of PC cells. Moreover, we found that PXN promoted the activation of the AKT signaling pathways which was involving in the cancer cells anoikis. Together, our findings reveal that miR-137 plays a novel role during anoikis and may serve as a potential target for the detection and treatment of PC.

Keywords: microRNA-137, paxillin, pancreatic cancer, anoikis