OncoTargets and Therapy (Oct 2020)
Long Non-Coding RNA LINC00511 Accelerates Proliferation and Invasion in Cervical Cancer Through Targeting miR-324-5p/DRAM1 Axis
Abstract
Xin Zhang,1 Yuyan Wang,2 Anqi Zhao,3 Fanshuang Kong,4 Lipeng Jiang,2 Jinfeng Wang5 1Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, People’s Republic of China; 3Capital Medical University, Beijing 100069, People’s Republic of China; 4Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, People’s Republic of China; 5Department of Pediatrics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, People’s Republic of ChinaCorrespondence: Jinfeng WangDepartment of Pediatrics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, People’s Republic of ChinaTel +86-13897836848Email [email protected]: Cervical cancer is the second most prevalent female malignance, and human papillomavirus (HPV) infection is the main pathogenic factor of cervical cancer. Emerging evidence has revealed that a number of long non-coding RNAs (lncRNAs) play critical roles in the tumorigenesis and progression of cervical cancer. The aim of this study was to further investigate the precise role of lncRNA LINC00511 in HPV-negative and HPV-positive cervical cancer cells and explore the potential regulatory mechanism.Methods: The expression of LINC00511 in cervical cancer and cell lines was examined by RT-PCR. Fluorescence in situ hybridization analysis (FISH) assay was performed to detect the localization of LINC00511 in cervical cancer cells. Loss-of-function experiments of LINC00511 by siRNA interference were performed to assess its effects on HPV-negative and HPV-positive cervical cancer cells. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to identify the target of LINC00511. Relative expression of related proteins was detected using Western blot.Results: Herein, the results showed that LINC00511 was significantly up-regulated in cervical cancer and cell lines and mainly distributed in the cytoplasm of cervical cancer cells. Loss-of-function experiments indicated that silencing of LINC00511 inhibited the proliferation and invasion of both HPV-negative and HPV-positive cervical cancer cells, as well as promoted apoptosis by regulating the Bcl-2/Bax axis and Caspase 3 activation. Bioinformatic analysis, dual-luciferase reporter, and RIP assays showed that LINC00511 was a target of miR-324-5p, while DRAM1 was a direct target of miR-324-5p. The expression of miR-324-5p was down-regulated in cervical cancer, while the expression of DRAM1 was up-regulated. Moreover, the expression of LINC00511 was negatively correlated with miR-324-5p expression in cervical cancer tissues and positively correlated with DRAM1. Further, DRAM1 overexpression promoted both HPV-negative and HPV-positive cervical cancer cell proliferation and invasion, which could be reversed by miR-324-5p mimics or si-LINC00511.Conclusion: Collectively, these results suggest that LINC00511 functions as a competing endogenous RNA (ceRNA) to regulate the miR-324-5p/DRAM1 axis, leading to HPV-negative and HPV-positive cervical cancer aggravation.Keywords: cervical cancer, LINC00511, HPV-negative, HPV-positive, miR-324-5p, DRAM1
