Abstract
Notably, a growing number of long noncoding RNAs (lncRNAs) have been recognized to play critical roles in hepatocellular carcinoma (HCC) progression. In this study, we identified a new lncRNA, Linc1749808 (ID: XR_001749808.1) based on microarray data from HCC tissues. Linc1749808 levels in 72 HCC tissues and paracancerous samples were detected by qRT-PCR. The interaction between Linc1749808 and microRNA-206 (miR-206) was assessed by bioinformatic analysis and luciferase assays. Linc1749808 depletion assays, Transwell assays, and miR-206-inhibitor rescue experiments were performed to examine the role of the Linc1749808/miR-206 axis in HCC cells. Our results showed that Linc1749808 was highly expressed in both HCC tissues and cell lines. Linc1749808 expression was significantly correlated with microvascular invasion, metastasis, and prognosis. After the knockdown of Linc1749808, the metastatic potential of 97H and HepG2 cells was attenuated in vitro and in vivo, but the proliferative capacity did not significantly change. Furthermore, Linc1749808 was found to act as a sponge of miR-206. Inhibition of miR-206 counteracted the effect of Linc1749808 knockdown in 97H cells by regulating YAP1 and epithelial-mesenchymal transition (EMT). In summary, these findings show that Linc1749808 can exacerbate the metastasis of HCC by sponging miR-206.
Highlights
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide [1]
To investigate the expression profile of Long noncoding RNAs (lncRNAs) in HCC, microarray analysis was performed on three pairs of liver cancer tissues and their adjacent non-tumor samples (Figures 1A, 1B)
Advances have been made in understanding the genomic changes in many cancers, the molecular mechanisms underlying the development of HCC are poorly understood [20]
Summary
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide [1]. The long noncoding RNA H19 can enhance HCC bone metastasis by reducing osteoprotegerin expression via PPP1CAinduced inactivation of the p38-MAPK pathway and the sequestration of miR-200b-3p [8]. The long noncoding RNA ZFPM2-AS1 can regulate miR-139 to promote HCC cell invasion [9]. Other analyses confirmed that lncRNAs can regulate tumor progression by sponging miR-206; for example, the lncRNA MIR4435-2HG functions as an oncogene in colorectal cancer in part by sponging miR-206 to upregulate the YAP1 expression and is likely to be a prognostic biomarker in colorectal cancer [12]. The present research verified that Linc1749808 facilitates EMT and progression in HCC by regulating the miR-206/YAP1 axis, and these results may provide a new direction for the effective prevention and treatment of HCC
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