miR-100-3p inhibits cell proliferation and induces apoptosis in human gastric cancer through targeting to BMPR2

Chun-Wei Peng; Ling-Xiao Yue; Yuan-Qin Zhou; Sai Tang; Chen Kan; Lei-Ming Xia; Fan Yang; Si-Ying Wang

doi:10.1186/s12935-019-1060-2

miR-100-3p inhibits cell proliferation and induces apoptosis in human gastric cancer through targeting to BMPR2

Cancer Cell Int. 2019 Dec 27:19:354. doi: 10.1186/s12935-019-1060-2. eCollection 2019.

Authors

Chun-Wei Peng¹, Ling-Xiao Yue¹, Yuan-Qin Zhou¹, Sai Tang¹, Chen Kan¹, Lei-Ming Xia¹, Fan Yang¹, Si-Ying Wang¹

Affiliation

¹ Department of Pathophysiology, School of Basic Medicine, Anhui Medical University, 81 MeiShan Road, Hefei, 230032 China.

Abstract

Background: miR-100 has been reported to closely associate with gastric cancer (GC) initiation and progression. However, the underlying mechanism of miR-100-3p in GC is still largely unclear. In this study, we intend to study how miR-100-3p regulates GC malignancy.

Methods: The expression levels of miR-100-3p in vitro (GES-1 and GC cell lines) and in vivo (cancerous and normal gastric tissues) were examined by quantitative real-time PCR (qRT-PCR). MTT and PE/Annexin V analyses were responsible for measurement of the effects of miR-100-3p on GC cell proliferation and apoptosis. Transwell assay with or without matrigel was used to examine the capacity of migration and invasion in GC cells. The interaction of miR-100-3p with bone morphogenetic protein receptor 2 (BMPR2) was confirmed through transcriptomics analysis and luciferase reporter assay. qRT-PCR and Western blot analyses were applied to determine the expression of ERK/AKT and Bax/Bcl2/Caspase3, which were responsible for the dysfunction of miR-100-3p.

Results: miR-100-3p was down-regulated in GC cell lines and cancerous tissues, and was negatively correlated with BMPR2. Loss of miR-100-3p promoted tumor growth and BMPR2 expression. Consistently, the effects of miR-100-3p inhibition on GC cells were partially neutralized by knockdown of BMPR2. Over-expression of miR-100-3p simultaneously inhibited tumor growth and down-regulated BMPR2 expression. Consistently, over-expression of BMPR2 partially neutralized the effects of miR-100-3p over-expression. Further study demonstrated that BMPR2 mediated the effects downstream of miR-100-3p, which might indirectly regulate ERK/AKT and Bax/Bcl2/Caspase3 signaling pathways.

Conclusion: miR-100-3p acted as a tumor-suppressor miRNA that down-regulated BMPR2, which consequently inhibited the ERK/AKT signaling and activated Bax/Bcl2/Caspase3 signaling. This finding provided novel insights into GC and could contribute to identify a new diagnostic and therapeutic target.

Keywords: B cell lymphoma-2 (Bcl2); Bone morphogenetic proteins receptor (BMPR2); Gastric cancer (GC); miR-100-3p.