Yuexun Xu1, Haiyan Zhu2, Hongbin Ma3, Lei Yuan4, Qunchao Hu5, Liang Yang5. 1. Department of Gynecology and Obstetrics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University Zhengzhou 450003, China. 2. Department of Gynaecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine Shanghai 201204, China. 3. Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital Shanghai, China. 4. The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital Shanghai, China. 5. Department of Radiation Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine Shanghai 201204, China.
Abstract
BACKGROUND: The association between LINC01305, a newly discovered long non-coding RNA (lncRNA), and cervical cancer (CC) has been poorly analyzed. In the present study, we revealed high expression of LINC01305 in CC by the cancer genome atlas (TCGA) and Gene Expression Omnibus (GEO), and dissected the related mechanisms. METHODS: LINC01305, microRNA (miR) -129-5p and SRY-related high-mobility group box 4 (Sox4) mRNA levels were quantitated by quantitative reverse transcription-PCRy qRT-PCR). CC tissues and cell lines and corresponding controls were enrolled for the quantification of LINC01305 expression in CC. Effects of LINC01305 and miR-129-5p on cell proliferation, metastasis, and apoptosis were evaluated by MTT, colony formation, wound healing, Transwell and flow cytometry assays. Sox4 protein levels were tested by Western blot (WB). Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and dual-luciferase reporter (DLR) assay were performed to determine molecular mechanisms of LINC01305 in CC. Xenograft models of CC were constructed to evaluate the role of LINC01305 in vivo. RESULTS: The expression of LINC01305 was evidently elevated in CC tissues and cell lines than that in controls and associated with clinicopathological features. Downregulating LINC01305 suppressed malignant phenotypes (proliferation, migration, invasion) of Hela and SiHa cells. In addition, silencing miR-129-5p by its inhibitor eliminated the inhibition of growth and metastasis induced by LINC01305 siRNA. Sox4 might serve as a direct target for miR-129-5p and was negatively regulated by miR-129-5p and LINC01305. CONCLUSION: LINC01305 acts as a competitive endogenous RNA (ceRNA) and regulates Sox4 via sponging miR-129-5p, contributing to the diagnosis and treatment of CC. AJTR
BACKGROUND: The association between LINC01305, a newly discovered long non-coding RNA (lncRNA), and cervical cancer (CC) has been poorly analyzed. In the present study, we revealed high expression of LINC01305 in CC by the cancer genome atlas (TCGA) and Gene Expression Omnibus (GEO), and dissected the related mechanisms. METHODS:LINC01305, microRNA (miR) -129-5p and SRY-related high-mobility group box 4 (Sox4) mRNA levels were quantitated by quantitative reverse transcription-PCRy qRT-PCR). CC tissues and cell lines and corresponding controls were enrolled for the quantification of LINC01305 expression in CC. Effects of LINC01305 and miR-129-5p on cell proliferation, metastasis, and apoptosis were evaluated by MTT, colony formation, wound healing, Transwell and flow cytometry assays. Sox4 protein levels were tested by Western blot (WB). Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and dual-luciferase reporter (DLR) assay were performed to determine molecular mechanisms of LINC01305 in CC. Xenograft models of CC were constructed to evaluate the role of LINC01305 in vivo. RESULTS: The expression of LINC01305 was evidently elevated in CC tissues and cell lines than that in controls and associated with clinicopathological features. Downregulating LINC01305 suppressed malignant phenotypes (proliferation, migration, invasion) of Hela and SiHa cells. In addition, silencing miR-129-5p by its inhibitor eliminated the inhibition of growth and metastasis induced by LINC01305 siRNA. Sox4 might serve as a direct target for miR-129-5p and was negatively regulated by miR-129-5p and LINC01305. CONCLUSION:LINC01305 acts as a competitive endogenous RNA (ceRNA) and regulates Sox4 via sponging miR-129-5p, contributing to the diagnosis and treatment of CC. AJTR
Authors: Angelina Huseinovic; Annelieke Jaspers; Annina P van Splunter; Hanne Sørgård; Saskia M Wilting; Dorian R A Swarts; Ida H van der Meulen; Victor W van Beusechem; Renée X de Menezes; Renske D M Steenbergen Journal: Int J Mol Sci Date: 2022-04-26 Impact factor: 6.208
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