Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence

Whole genome transcriptomic analyses have iden- tified a large number of long non-coding RNAs (lncRNAs), many of which are involved in a variety of biological func- tions. However, their functions and molecular mechanisms associated with prostate cancer (PCa) progression to a viru- lent and androgen-independent (AI) form remain elusive. Herein, we investigated the lncRNA expression profiles of the indolent, androgen-dependent (AD) LNCaP cell line to the aggressive metastatic, AI C4-2 cell line using micro- array technology. The differentially expressed lncRNAs and genes were identified by microarray technology and the association in cis or in trans was analyzed to find potential lncRNA target genes. Expression of candidate lncRNAs and putative targets was evaluated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The functions of linc00963 on cell proliferation, apoptosis, migration and invasion were evaluated by a knockdown strategy in vitro using MTT, flow cytometric analysis and transwell chamber assays. lncRNAs (n=134) were differen- tially expressed (FDR <0.001 and fold change ≥2) between the LNCaP and C4-2 cell lines. Linc00963 was upregulated most obviously evaluated by qRT-PCR. Knockdown of linc00963 attenuated C4-2 cell proliferation, motility, inva- sion ability, the expression of EGFR and phosphorylation levels of AKT, and promoted cell apoptosis. Linc00963 was involved in the prostate cancer transition from androgen- dependent to androgen-independent and metastasis via the EGFR signaling pathway.