Abstract
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.
Highlights
Long noncoding RNA, urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene
We further found that the UCA1-miR145-Myosin VI (MYO6) pathway plays a vital role in Gastric cancer (GC) cell proliferation and apoptosis, which may be valuable as a potential remedial target in GC
UCA1 is enriched in serum exosomes from patients with GC In this study, serum samples from 85 GC patients and 50 healthy individuals were collected, and exosomes were isolated from the serum
Summary
Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. The underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. We aimed to identify how UCA1 promotes gastric cancer development. Further insights into the molecular mechanisms underlying GC development may help discover potential therapeutic targets. Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides and lacking protein-coding potential, which play critical roles in numerous biological processes, including cancer development. Accumulating evidence has demonstrated that lncRNAs function as tumor suppressor genes or oncogenes to influence cancer cell proliferation, apoptosis, invasion, or migration [3]. The lncRNA, urothelial carcinoma associated 1 (UCA1), located at the human chromosome 19p13.12, was discovered in bladder cancer. Previous reports have indicated that highUCA1 expression might exert an oncogenic effect in the pathogenic process of GC and act as a diagnostic and prognostic biomarker [7], the precise pathophysiological functions and detailed signaling pathways of UCA1 in GC remain to be determined
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