Cancer Management and Research (Sep 2020)
Long Non-Coding RNA DARS-AS1 Contributes to Prostate Cancer Progression Through Regulating the MicroRNA-628-5p/MTDH Axis
Abstract
Haitao Fan,1 Junhui Hou,2 Siqing Liu,3 Zuomin Xiao,4 Jia Cui5 1Department of Urology, The Second Hospital of Jilin University, Changchun, Jilin 130041, People’s Republic of China; 2Department of Oncology & Radiotherapy, Qingdao Central Medical Group, Qingdao, Shandong 266000, People’s Republic of China; 3Department of Outpatient, Qingdao Special Service Sanatorium of PLA Navy, Qingdao, Shandong 266071, People’s Republic of China; 4Department of Clinical Laboratory, Jinan Jigang Hospital, Jinan, Shandong 250101, People’s Republic of China; 5Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116023, People’s Republic of ChinaCorrespondence: Jia CuiDepartment of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116023, People’s Republic of ChinaEmail [email protected]: DARS antisense RNA 1 (DARS-AS1) is a long non-coding RNA that has been validated as a critical regulator in several human cancer types. Our study aimed to determine the expression profile of DARS-AS1 in prostate cancer (PCa) tissues and cell lines. Functional experiments were conducted to explore the detailed roles of DARS-AS1 in regulating PCa carcinogenesis. Furthermore, the detailed mechanisms by which DARS-AS1 regulates the oncogenicity of PCa cells were uncovered.Methods: Reverse transcription quantitative polymerase chain reaction was performed to analyze DARS-AS1 expression in PCa tissues and cell lines. Cell Counting Kit-8 assays, flow cytometry analyses, Transwell assays, and tumor xenograft experiments were conducted to determine the regulatory effects of DARS-AS1 knockdown on the malignant phenotype of PCa cells. Bioinformatics analysis was performed to identify putative microRNAs (miRNAs) targeting DARS-AS1, and the direct interaction between DARS-AS1 and miR-628-5p was verified using RNA immunoprecipitation and luciferase reporter assays.Results: DARS-AS1 was highly expressed in PCa tissues and cell lines. In vitro functional experiments demonstrated that DARS-AS1 depletion suppressed PCa cell proliferation, promoted cell apoptosis, and restricted cell migration and invasion. In vivo studies revealed that the downregulation of DARS-AS1 inhibited PCa tumor growth in nude mice. Mechanistic investigation verified that DARS-AS1 functioned as an endogenous miR-628-5p sponge in PCa cells and consequently promoted the expression of metadherin (MTDH). Furthermore, the involvement of miR-628-5p/MTDH axis in DARS-AS1-mediated regulatory actions in PCa cells was verified using rescue experiments.Conclusion: DARS-AS1 functioned as a competing endogenous RNA in PCa by adsorbing miR-628-5p and thereby increasing the expression of MTDH, resulting in enhanced PCa progression. The identification of a novel DARS-AS1/miR-628-5p/MTDH regulatory network in PCa cells may offer a new theoretical basis for the development of promising therapeutic targets.Keywords: DARS antisense RNA 1, non-coding RNA, ceRNA theory, target therapy
