Long Non-Coding RNA (LncRNA) Urothelial Carcinoma Associated 1 (UCA1) Increases Multi-Drug Resistance of Gastric Cancer via Downregulating miR-27b

Abstract

BackgroundIn this study, we aimed to investigate the association between UCA1 and miR-27b in gastric cancer and further study their involvement in multi-drug resistance (MDR) of gastric cancer.Material/MethodsThe microarray data of dysregulated lncRNAs in gastric cancer tissues was retrieved in the GEO dataset. QRT-PCR analysis was performed to assess UCA1 expression based on 28 paired cancerous and peritumoral normal tissues. The human gastric cancer cell line SGC-7901, and SGC-7901 derived Adriamycin (doxorubicin) resistant SGC-7901/ADR, cisplatin resistant SGC-7901/DDP, and 5-FU resistant SGC-7901/FU cells were used as in vitro cell models to assess the effect of UCA1 and miR-27b on MDR.ResultsUCA1 was significantly upregulated in the cancerous tissues and its expression was negatively correlated with miR-27b expression level. Inhibition of UCA1 significantly restored miR-27b expression in MDR gastric cancer cells. UCA1 knockdown and miR-27b overexpression reduced IC50 of ADR, DDP, and 5-FU in SGC-7901/ADR cells and increased ADR induced cell apoptosis. UCA1 overexpression and miR-27b inhibition increased the IC50 of ADR, DDP, and 5-FU in SGC-7901 cells and reduced ADR induced cell apoptosis. Western blot analysis showed that UCA1 knockdown and miR-27b overexpression also decreased anti-apoptotic protein BCL-2 and increased apoptotic protein cleaved caspase-3.ConclusionsUCA1 is negatively correlated with miR-27b expression in gastric cancer tissue. Knockdown of UCA1 restored miR-27b expression in gastric cancer cells. The UCA1-miR-27b axis was involved in regulation of chemosensitivity of gastric cancer cells.

Retracted: Knockdown of long noncoding RNA urothelial carcinoma–associated 1 inhibits cell viability, migration, and invasion by regulating microRNA‐182 in gastric carcinoma

“…24,25 One study reported that UCA1 silencing impaired lung cancer cell proliferation and colony formation by regulation of miR-193a-3p. 27 Further, Fang et al 28 found that UCA1 could increase the multidrug resistance of GC through downregulation of miR-27b. 27 Further, Fang et al 28 found that UCA1 could increase the multidrug resistance of GC through downregulation of miR-27b.…”

Crosstalk between the lncRNA UCA1 and microRNAs in cancer

“…Furthermore, UCA1 could sponge the miR-590-3p targeting cyclic adenosine monophosphate response element-binding protein 1 (CREB1), and knockdown of CREB1 inhibits the growth of human GC in vitro and in vivo [67,68]. Moreover, UCA1 increased multi-drug resistance of GC by downregulating miR-27b [69]. Colon cancer is one of the most common cancers in the world, characterized by unlimited proliferation and high metastasis [70].…”

RNA-Sequencing Data Reveal a Prognostic Four-lncRNA-Based Risk Score for Bladder Urothelial Carcinoma: An in Silico Update

“…It has been experimentally validated that lncRNAs are involved in the etiology and pathogenesis of various cancers, including BLCA [13][14][15][16][17][18][19][20]. The recent advances in high-throughput data technologies, including RNAsequencing and microarrays, has guided the identification of lncRNAs for prospective clinical application in BLCA [12,[21][22][23]. However, most previous studies focused on the clinical value of individual lncRNAs, which has limited potential for future clinical application.…”