Abstract
Noncoding RNAs plays an important role in hepatocellular carcinoma (HCC). Here, we show that miR-124 was downregulated in HCC tissues and that the ectopic expression of miR-124 inhibited the proliferation and migration of HCC cells. We proposed that aquaporin 3 (AQP3) is a direct target of miR-124. AQP3 was upregulated in HCC tissues and inversely correlated with miR-124 expression. The overexpression of miR-124 decreased AQP3 expression. Indeed, AQP3 overexpression promoted cell proliferation and migration, whereas miR-124 knockdown suppressed cell proliferation and migration. Furthermore, we found that circular RNA HIPK3 (circHIPK3) acted as a miR-124 sponge and regulated the expression of the miR-124 target gene AQP3. circHIPK3 was upregulated in HCC tissues and positively correlated with AQP3 expression. Thus, silencing circHIPK3 inhibited cell proliferation and migration by downregulating AQP3 expression. Moreover, miR-124 inhibition rescued circHIPK3 knockdown induced reduction in cell proliferation and migration, as well as AQP3 expression. In vivo experiments also confirmed that circHIPK3 regulated xenograft tumor growth via the miR-124-AQP3 axis. These observations indicate a possible novel therapeutic strategy involving circular RNAs in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fifth leading and the second-most lethal carcinoma worldwide[1]
Given the elevated expression of miR-124 in hepatocellular carcinoma (HCC) tissues, we explored miR-124 expression in HCC cell lines (Huh[7], MHCC-LM3, HepG2, SMMC-7721, and PLC) and the hepatocyte cell line HL-7702 (L02) and found that miR-124 was downregulated in HCC cells (Fig. 1b)
After establishing that circHIPK3 can bind with miR124 and is positively correlated with aquaporin 3 (AQP3) expression, we proposed that circHIPK3 serves the same role in HCC
Summary
Hepatocellular carcinoma (HCC) is the fifth leading and the second-most lethal carcinoma worldwide[1]. Recent studies have demonstrated the important role of AQPs in tumorigenesis and cancer progression[5,6]. MiR-21 promotes the proliferation, migration, and invasion of HCC cells by targeting PTEN9. CircPVT1 is upregulated in gastric cancer (GC), and promotes cell proliferation by acting as a sponge for the miR-125. We found that miR-124 could mediate the proliferation and migration of HCC cells by targeting. Considering the novel function of circRNAs in cancer biology, we proposed that the downregulation of miR-124 may be mediated by circRNAs24. We further identified circHIPK3 as being upregulated in HCC and showed that it could promote cell proliferation and migration through AQP3 by sponging miR-124. The present study is the first to provide evidence regarding the interactions among miR-124, AQP3, and circHIPK3 in HCC, thereby identifying the potential of this axis for cancer treatment
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