miR-92b-3p acts as a tumor suppressor by targeting Gabra3 in pancreatic cancer

Molecular Cancer

Research

Sunwang Xu¹  Jian Wang¹  Wei Chen¹  Ming Zhan¹  Ruimeng Yang¹  Man Mohan²  Qiang Liu³  Shilei Zhang³  Qiao He³  Yongheng Shi³  Manmei Long⁴ 

[1] Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China;Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Institutes of Medical Sciences, Shanghai Jiao Tong University, School of Medicine, 200025, Shanghai, China;Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China;Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China;Department of Pathology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 200011, Shanghai, China;

关键词: MiR-92b-3p;    Pancreatic cancer;    Gabra3;    Tumor proliferation and metastasis;   

DOI  :  10.1186/s12943-017-0723-7

 received in 2016-11-20, accepted in 2017-09-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) can act as oncogenes or tumor suppressors by controlling cell proliferation, differentiation, metastasis and apoptosis, and miRNA dysregulation is involved in the development of pancreatic cancer (PC). Our previous study demonstrated that Gabra3 plays critical roles in cancer progression. However, whether Gabra3 is regulated by miRNAs in PC remains unknown.MethodsThe expression levels of miR-92b-3p and Gabra3 were measured by quantitative PCR (qPCR), immunoblotting, in situ hybridization (ISH) and immunohistochemistry (IHC). The proliferation rate of PC cells was detected by MTS assay. Wound-healing and transwell assays were used to examine the invasive abilities of PC cells. Dual-luciferase reporter assays were used to determine how miR-92b-3p regulates Gabra3. Xenograft mouse models were used to assess the role of miR-92b-3p in PC tumor formation in vivo.ResultsHere, we provide evidence that miR-92b-3p acted as a tumor suppressor in PC by regulating Gabra3 expression. MiR-92b-3p expression levels were lower in PC tissues than corresponding noncancerous pancreatic (CNP) tissues and were associated with a poor prognosis in PC patients. MiR-92b-3p overexpression suppressed the proliferation and invasion of PC cells in both in vivo and in vitro models. Conversely, miR-92b-3p knockdown induced an aggressive phenotype in PC cells. Mechanistically, miR-92b-3p overexpression suppressed Gabra3 expression, which then led to the inactivation of important oncogenic pathways, including the AKT/mTOR and JNK pathways.ConclusionOur results suggest that miR-92b-3p acted as a tumor suppressor by targeting Gabra3-associated oncogenic pathways; these results provide novel insight into future treatments for PC patients.

【 授权许可】

CC BY   
© The Author(s). 2017