OncoTargets and Therapy (Mar 2021)
LncRNA KCNQ1OT1 Promotes Proliferation, Invasion and Metastasis of Prostate Cancer by Regulating miR-211-5p/CHI3L1 Pathway
Abstract
Hailong Hao,1 Huiqing Chen,1 Liwu Xie,2 Hongyu Liu,1 Dongwen Wang3 1Department of Urology, Shanxi Cancer Hospital, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pathology, Shanxi Cancer Hospital, Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of ChinaCorrespondence: Dongwen Wang Email [email protected]: Bone metastasis after failure of castration therapy is the main reason of death in patients with prostate cancer (PCa). Therefore, full awareness of the metastasis mechanism of PCa and discovery of new therapeutic targets are necessary. Studies showed that lncRNA was involved in the development of cancer. However, its potential role and molecular mechanism in PCa metastasis are still unclear. YKL-40 is an 18 glycosyl hydrolase family protein encoded by CHI3L1, which is involved in the invasion and metastasis of various tumors. A previous study of the authors found that YKL-40 was related to the invasion and metastasis of PCa cells. However, the cause of its abnormal expression in PCa remains unclear. The present study explored the role of lncRNA KCNQ1OT1/miR-211-5p/CHI3L1 regulatory axis in the proliferation, invasion, and metastasis of PCa.Methods: RT-PCR and Western blot were used to measure the expression profiles of KCNQ1OT1 and YKL. CCK-8 and Transwell assays were used to examine their effects on cell proliferation and migration. Double luciferase reporter assay was used to verify the interactions between miR-211-5p and CHI3L1 3′-UTR.Results: KCNQ1OT1 expression was upregulated in PCa tissues and cells. Downregulating this expression inhibited PCa cell invasion, proliferation, and metastasis. KCNQ1OT1 bound miR-211-5p competitively, and miR-211-5p targeted CHI3L1 3′-UTR. miR-211-5p expression was downregulated, whereas CHI3L1 (YKL-40) expression was upregulated. miR-211-5p levels were negatively correlated with KCNQ1OT1 expression and CHI3L1 mRNA. The decrease in YKL-40 expression in PCa cells induced by the downregulation of KCNQ1OT1 expression could be offset by miR-211-5p inhibitor transfection.Conclusion: This study showed that lncRNA KCNQ1OT1, as a ceRNA, upregulated CHI3L1 and promoted PCa progression through competitive binding to miR-211-5p.Keywords: prostatic cancer, PCa, lncRNA KCNQ1OT1, miR-211-5p, CHI3L1, competing endogenous RNA
