Knockdown of long noncoding RNA urothelial carcinoma associated 1 inhibits colorectal cancer cell proliferation and promotes apoptosis via modulating autophagy

• Published in: Journal of cellular physiology 2019-05, Vol.234 (5), p.7420-7434
• Main Authors: Song, Fengling, Li, Lexing, Liang, Danyang, Zhuo, Yisha, Wang, Xueyi, Dai, Hanchuan
• Format: Article
• Language: English
• Subjects: AKT protein; Apoptosis; Autophagy; Autophagy-Related Protein 5 - genetics; Autophagy-Related Protein 5 - metabolism; Bladder cancer; Caco-2 Cells; Cancer; Cell activation; Cell Cycle; Cell growth; Cell Proliferation; Cell survival; Colorectal cancer; colorectal cancer (CRC) cell; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Correlation analysis; Down-Regulation; G1 phase; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; HCT116 Cells; HEK293 Cells; HT29 Cells; Humans; Kinases; Light levels; long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1); Metastases; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Phages; Phagocytosis; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rapamycin; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sequestosome-1 Protein - genetics; Sequestosome-1 Protein - metabolism; Signal Transduction; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumorigenesis; Urothelial carcinoma
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27500

Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been implicated in the growth and metastasis of colorectal cancer (CRC), and autophagy contributes to tumorigenesis and cancer cell survival. However, the regulatory role of UCA1 in CRC cell viability by modulating autophagy remains unclear. In the present study, a significant positive correlation was observed between UCA1 and microtubule‐associated protein 1 light chain 3 (LC3) levels, and the elevated UCA1 was negatively correlated with the PKB/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in 293T cells. Downregulation of UCA1 inhibited autophagy activation and cell proliferation, whereas the apoptosis was increased and the cell cycle was arrested in G2 stage. The next results showed that UCA1 was markedly upregulated in Caco‐2 cells. Knockdown of UCA1 significantly decreased the LC3‐II and autophagy‐related gene 5 (ATG5) protein levels and resulted in an increase in p62 expression. Conversely, the autophagy activator rapamycin (RAPA) reversed the effects. Furthermore, downregulated UCA1 decreased Caco‐2 cells population in the G1 phase and increased the cells number in G2 phage. The cell proliferation was inhibited, and apoptosis rate was promoted. More important, RAPA could also abrogate the changes induced by knockdown of UCA1. Collectively, these data demonstrated that downregulated UCA1 induced autophagy inhibition, resulting in suppressing cell proliferation and promoting apoptosis, which suggested that UCA1 might serve as a potential new oncogene to regulate CRC cells viability by modulating autophagy. Downregulated urothelial carcinoma associated 1 (UCA1) induced autophagy inhibition, resulting in suppressing cell proliferation and promoting apoptosis. The data suggested that UCA1 might serve as a potential new oncogene to regulate colorectal cancer (CRC) cells viability by modulating autophagy.