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.

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that play an important role in cancer. However, the mechanisms by which circRNAs regulate gene expression in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study seeks to elucidate the role that circRNAs play in the proliferation of PDAC cells. On the basis of previous studies of circRNA expression profiles in PDAC, we found that the circRNA_100782 was markedly upregulated in PDAC tissue. Functional experiments revealed that circRNA_100782 down-regulation inhibited BxPC3 cell proliferation and colony formation. Loss-of-function studies showed that knockdown of circRNA_100782 inhibited cell proliferation by downregulating the microRNA-124 (miR-124) target genes interleukin-6 receptor (IL6R) and signal transducer and activator of transcription 3 (STAT3). Overexpression of miR-124 also inhibited BxPC3 cell proliferation by reducing the expression of IL6R and STAT3, which was consistent with the result of silencing circRNA_100782. In addition, luciferase assay revealed that miR-124 was a direct target of circRNA_100782. Silencing STAT3 inhibited BxPC3 cell proliferation and colony formation. Cell viability was reduced in BxPC3 cells treated with si-circRNA_100782 and miR-124 mimic, and this effect could be attenuated by activating STAT3. In vivo study validated that circRNA_100782 knockdown suppressed BxPC3 xenografts in nude mice. Taken together, these results suggest that circRNA_100782 regulates BxPC3 cell proliferation by acting as miR-124 sponge through the IL6–STAT3 pathway.