LncRNA DGCR5 represses the development of hepatocellular carcinoma by targeting the miR‐346/KLF14 axis

Abstract

Long non-coding RNAs (lncRNAs) are a class of regulatory noncoding RNAs. Emerging evidence highlights the critical roles of lncRNAs in the progression of hepatocellular carcinoma (HCC). Although many lncRNAs have been identified in the development of HCC, the association between DiGeorge syndrome critical region gene 5 (DGCR5) and HCC remains unclear. In the current study, we focused on the biological role of DGCR5 in HCC. We observed that DGCR5 was decreased in HCC cells, including SMCC7721, Hep3B, HepG2, MHCC-97L, MHCC-97H, and SNU449 hepatocellular carcinoma cells, compared with the normal human liver cell line THLE-3 normal human liver cells. In addition, DGCR5 overexpression could repress HCC cell growth, migration, and invasion considerably. Increasing studies have indicated the interactions between lncRNAs and microRNAs. MicroRNAs are endogenous small noncoding RNAs and they can play important roles in tumorigenesis. MicroRNA 346 (miR-346) has been demonstrated in various human cancer types, including HCC. MiR-346 was found to be increased in HCC cells and DGCR5 can act as a sponge of miR-346 to modulate the progression of HCC. The binding correlation between DGCR5 and miR-346 was validated in our research. Subsequently, Krüppel-like factor 14 (KLF14) was predicted as a downstream target of miR-346 and miR-346 can induce the development of HCC by inhibiting KLF14. Finally, we proved that DGCR5 can rescue the inhibited levels of KLF14 repressed by miR-346 mimics in MHCC-97H and Hep3B cells. Taken together, it was indicated in our study that DGCR5 can restrain the progression of HCC through sponging miR-346 and modulating KLF14 in vitro.

<p>LncRNA ASB16-AS1 Promotes Growth And Invasion Of Hepatocellular Carcinoma Through Regulating miR-1827/FZD4 Axis And Activating Wnt/β-Catenin Pathway</p>

“…25 In addition, lncRNA DGCR5 inhibits HCC cell proliferation and invasion via sponging miR-346 and activating KLF14. 26 However, how ASB16-AS1 exerts roles remains unclear. In our study, after bioinformatics prediction, we identified ASB16-AS1 may interact with miR-1827.…”

Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis

“…In contrast, lncRNA DGCR5 (DiGeorge syndrome critical region gene 5) was found to be down-regulated in HCC tissues. Overexpressing the lncRNA DGCR5 inhibits the development of HCC by targeting the miRNA-346/KLF14 axis [12]. In the present study, we demonstrated that the knockdown of RP11-284P20.2 is associated with suppressed viability, migration, invasion and colony formation and increased apoptosis of HCC cells.…”

“…Various biological functions of lncRNAs have been identified. For instance, lncRNAs can act as competing endogenous RNAs (ceRNA) of endogenous miRNAs, which prevents the binding of the miRNAs to their target mRNAs [12]. In addition, lncRNAs are also associated with epigenetic regulation as they can interact with several methylases and acetylases [13].…”

Long non‐coding RNA SUMO1P3 promotes hepatocellular carcinoma progression through activating Wnt/β‐catenin signalling pathway by targeting miR‐320a

“…For example, Zhu et al found that lncRNA NEAT1 interacting with miR‐384 contributed to HCC progression via promoting cell proliferation, migration and invasion. Wang et al demonstrated that lncRNA DGCR5 exerted suppressive function in HCC progression through miR‐346/KLF14 axis. lncRNAs are involved in various biological processes in HCC tumorigenesis, and may be employed as therapeutic targets, thus improving clinical outcomes of the patients.…”