Lncrna Paint Promotes Prostate Cancer Progression Through Modulation Of Genes Involved In Epithelial-Mesenchymal Transition And Apoptosis.

Abstract Long non-coding RNAs (LncRNAs) play regulatory roles in cellular processes and their aberrant expression may drive cancer progression. Here we report the function of a LncRNA PAINT (Prostate Cancer-Associated Intergenic Non-Coding Transcript) in promoting prostate cancer (PCa) progression. Upregulation of PAINT expression was noted in the advanced stage and metastatic PCa patient tissues and correlated with poor survival. Inhibition of PAINT decreased cell proliferation, S-phase progression, increased expression of apoptotic markers, and improved sensitivity to docetaxel and Aurora kinase inhibitor VX-680. Inhibition of PAINT also decreased cell migration and reduced expression of mesenchymal markers, Slug, and Vimentin. Ectopic expression of PAINT suppressed E-cadherin, increased S-phase progression, and cell migration. PAINT expression in PCa cells also induced larger colony formation and higher expression of mesenchymal markers. Transcriptome profiling of PCa cells overexpressing PAINT showed differential expression of genes involved in epithelial-mesenchymal transition (EMT), apoptosis, and drug resistance which were further validated by qRT-PCR analysis. Additionally, GO enrichment and KEGG pathway analysis revealed altered expression of multiple pathways including p53 signaling and drug metabolism pathways indicating that PAINT may promote an oncogenic environment by simultaneously regulating various biological processes in PCa. In summary, our findings establish the role of PAINT as an oncogene in PCa and indicate the clinical significance of PAINT as a diagnostic marker and a possible therapeutic target for aggressive PCa. Citation Format: Kavya Ganapathy, Md Faqrul Hasan, Jiao Sun, Ayman Khatib, Thomas Andl, Julia Soulakova, Domenico Coppola, Wei Zhang, Ratna Chakrabarti. LncRNA PAINT promotes prostate cancer progression through modulation of genes involved in epithelial-mesenchymal transition and apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2390.