Hasan Md Faqrul, Ganapathy Kavya, Sun Jiao, Khatib Ayman, Andl Thomas, Soulakova Julia N, Coppola Domenico, Zhang Wei, Chakrabarti Ratna
Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, USA.
Department of Computer Science, University of Central Florida, Orlando, Florida, USA.
Int J Cancer. 2021 Mar 17. doi: 10.1002/ijc.33569.
Long noncoding RNAs (lncRNAs) play regulatory role in cellular processes and their aberrant expression may drive cancer progression. Here we report the function of a lncRNA PAINT (prostate cancer associated intergenic noncoding transcript) in promoting prostate cancer (PCa) progression. Upregulation of PAINT was noted in advanced stage and metastatic PCa. 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 decreased cell migration and reduced expression of Slug and Vimentin. Ectopic expression of PAINT suppressed E-cadherin, increased S-phase progression and cell migration. PAINT expression in PCa cells induced larger colony formation, increased tumor growth and higher expression of mesenchymal markers. Transcriptome analysis followed by qRT-PCR validation showed differentially expressed genes involved in epithelial mesenchymal transition (EMT), apoptosis and drug resistance in PAINT-expressing cells. Our study establishes an oncogenic function of PAINT in PCa.
长链非编码RNA(lncRNAs)在细胞过程中发挥调节作用,其异常表达可能推动癌症进展。在此,我们报告一种lncRNA PAINT(前列腺癌相关基因间非编码转录本)在促进前列腺癌(PCa)进展中的功能。在晚期和转移性PCa中观察到PAINT上调。抑制PAINT可降低细胞增殖、S期进程,增加凋亡标志物的表达,并提高对多西他赛和极光激酶抑制剂VX-680的敏感性。抑制PAINT可减少细胞迁移,并降低Slug和波形蛋白的表达。PAINT的异位表达抑制E-钙黏蛋白,增加S期进程和细胞迁移。PCa细胞中PAINT的表达诱导更大的集落形成、增加肿瘤生长以及间充质标志物的更高表达。转录组分析随后进行qRT-PCR验证,结果显示在表达PAINT的细胞中,参与上皮-间质转化(EMT)、凋亡和耐药的基因表达存在差异。我们的研究确立了PAINT在PCa中的致癌功能。