OncoTargets and Therapy (Nov 2020)
LncRNA CTBP1-AS2 Facilitates Gastric Cancer Progression via Regulating the miR-139-3p/MMP11 Axis
Abstract
Yudan Yang,1 Ming Gao,1 Yunpeng Li,2 Mengyi Li,1 Qingqing Ma1 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of ChinaCorrespondence: Yudan Yang Email [email protected]: This study aimed at probing into the effect of long non-coding RNA (lncRNA) C-terminal binding protein 1 antisense RNA 2 (CTBP1-AS2) on gastric cancer (GC) cell proliferation and apoptosis, and its regulatory function on miR-139-3p and MMP11.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to examine the expressions of CTBP1-AS2, miR-139-3p and MMP11 mRNA in GC cell lines and clinical specimens. Cell counting kit-8 (CCK-8) assay, flow cytometry and EdU assay were conducted to examine the effects of CTBP1-AS2 and miR-139-3p on GC cell proliferation and apoptosis. Western blot was applied for detecting the expressions of Bax, Bcl-2 and MMP11. A lung metastasis mouse model was used to evaluate metastasis of GC cells in vivo. Bioinformatics, dual-luciferase report assay, RIP and RNA pull-down assays were utilized to validate the targeted relationship between CTBP1-AS2 and miR-139-3p as well as the targeting relationship between miR-139-3p and MMP11.Results: CTBP1-AS2 was highly expressed in GC, and its high expression was strongly associated with increased TNM stage, increased tumor size and low degree of differentiation of the tumor tissues. Meanwhile, CTBP1-AS2 promoted GC cell proliferation, metastasis and suppressed apoptosis, while miR-139-3p could weaken these effects. In addition, CTBP1-AS2 was identified as a molecular sponge for miR-139-3p, and MMP11 was verified as a target gene of CTBP1-AS2. CTBP1-AS2 could increase the expression of MMP11 via repressing miR-139-3p.Conclusion: CTBP1-AS2 promotes GC cells and inhibits apoptosis by regulating the miR-139-3p/MMP11 molecular axis.Keywords: CTBP1-AS2, GC, proliferation, apoptosis
