LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis

Cellular & Molecular Biology Letters

Xin Liu¹  Ping Liu²  Xinyan Han²  Yunzhang Feng²  Hongbo Liu²  Jurong Wang²  An Yang²  Wei Kong²  Shen Gao³  Limin Huo³ 

[1] Affiliated Hospital of Hebei University of Engineering, 056002, Handan, Hebei Province, China;Handan Central Hospital, 056001, Handan, Hebei Province, China;Handan First Hospital, 056002, Handan, Hebei Province, China;

关键词: Gastric cancer;    lncRNA;    UCA1;    miR-145;    MYO6;   

DOI  :  10.1186/s11658-021-00275-8

来源: Springer

【 摘 要 】

BackgroundLong noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development.MethodsThe Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation.ResultsUCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells.ConclusionsUCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

【 授权许可】

CC BY