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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2018.00554

RAB31 targeted by MiR-30c-2-3p regulates the GLI1 Signaling Pathway, affecting Gastric Cancer Cell Proliferation and Apoptosis

 Chao-Tao Tang1, Qian Liang1, Li Yang1, Xiao-Lu Lin2, Shan Wu1, Yong Chen1, Xin-Tian Zhang1, Yun-Jie Gao1 and Zhi-Zheng Ge1*
  • 1Renji Hospital, Shanghai JiaoTong University School of Medicine, China
  • 2Fujian Provincial Hospital, China

Background:Gastric cancer (GC), one of the most common cancers worldwide, is highly malignant and fatal. RAB31, a member of the RAB family of oncogenes, participates in the process of carcinogenesis and cancer development. However, the underlying role of RAB31 in GC progression remains unknown.
Methods:In our study, 90 pairs of tissue microarrays were used to measure the level of RAB31 protein by immunochemistry assay and 22 pairs of fresh tissue were used to measure the level of RAB31 mRNA. We investigated the effect of RAB31 on tumor growth in vitro and in vivo.
Results: RAB31 was overexpressed in GC tissues, and the overexpression of RAB31 predicted poor survival. In a nude mouse model, we found that depletion of RAB31 inhibited tumor growth. In vitro, silencing of RAB31 suppressed cell viability, promoted cell cycle arrest, and enhanced cell apoptosis. Further, cell cycle and apoptotic protein expression was subsequently reduced; these effects were mediated by GLI1. More importantly, co-IP and Immunofluorescence assays confirmed that RAB31 interacted with GLI1. In addition, via luciferase reporter assay and Western blotting, we found that miR-30c-2-3p modulates the RAB31/GLI1 pathway through the targeting of the 3’-UTR of RAB31.
Conclusions: Collectively, these data show that RAB31 was regulated by miR-30c-2-3p and functioned as an oncogene in GC tumorigenesis and development via interacting with GLI1. Therefore, the targeting of miR-30c-2-3p/RAB31/GLI1 axis may be regarded as a therapeutic intervention in gastric cancer.

Keywords: Rab31, GLI1, miR-30c-2-3p, Gastric cancer,, prognosis, proliferation

Received: 16 Aug 2018; Accepted: 08 Nov 2018.

Edited by:

Pashtoon M. Kasi, Mayo Clinic, United States

Reviewed by:

Qingfeng Zhu, Johns Hopkins Medicine, United States
Toru Furukawa, School of Medicine, Tohoku University, Japan  

Copyright: © 2018 Tang, Liang, Yang, Lin, Wu, Chen, Zhang, Gao and Ge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Zhi-Zheng Ge, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China, zhizhengge@aliyun.com