Downregulation of LncRNAH19 and MiR-675 promotes migration and invasion of human hepatocellular carcinoma cells through AKT/GSK-3β/Cdc25A signaling pathway

Abstract

LncRNAH19 has been implicated as having both oncogenic and tumor suppression properties in cancer. LncRNAH19 transcripts also serve as a precursor for miR-675. However, it is unknown whether LncRNAH19 and miR-675 are involved in the migration and invasion of hepatocellular carcinoma (HCC) cells. The purpose of this study was to investigate the effect and mechanism of LncRNAH19 and miR-675 on migration and invasion of HCC cells. The migration and invasion of HCC cells were measured by Transwell migration and invasion assays after transfection of HCC cells with miR-675 inhibitors and LncRNAH19siRNA. The levels of LncRNAH19 and miR-675 were detected by quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR), and the protein expression of AKT, GSK-3β and Cdc25A by Western blotting analysis. The expression levels of LncRNAH19 and miR-675 were higher in MHCC-97H cells than in L02, Huh-7 and HepG2 cells. Transwell migration assay revealed that the miR-675 inhibitor and LncRNAH19siRNA could significantly increase the migration of HCC cells (P<0.01) as compared with the control group. Transwell invasion assay demonstrated that the miR-675 inhibitor and LncRNAH19siRNA could significantly increase the invasion of HCC cells (P<0.01) as compared with the control group. Western blotting analysis showed that the expression levels of AKT and Cdc25A were significantly increased (P<0.05), and the expression level of GSK-3β was significantly decreased (P<0.05) after treatment with miR-675 inhibitors and LncRNAH19siRNA as compared with the control group. These findings suggested that inhibition of LncRNAH19 and miR-675 expression can promote migration and invasion of HCC cells via AKT/GSK-3β/Cdc25A signaling pathway.

Effects of LncRNA-HOST2 on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma cell line SMMC-7721

“…Also, results of experiments on cells verified that the increased expression of HOST2 increased cell proliferation, as well as cell migration and invasion, which was consistent with previous study that the increased expression of LncRNA in HCC tissues was mainly related to the invasion of HBV [19]. Multiple LncRNAs are demonstrated to be correlated to HCC, Wang et al [20] indicated that LncRNA-UCA1 up-regulation promotes HCC progression accompanied by miR-216b inhibition, and Lv et al showed that LncRNA H19 and miR-675 inhibition contributes to migration and invasion of HCC [21]. HOST2 is a novel gene that contains plentiful copies of retroviral-related sequences [14].…”

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

“…It has also been demonstrated that multiple LncRNAs are associated with HCC. For example, Wang et al revealed that LncRNA-UCA1 upregulation and miR-216b inhibition could promote the progression of HCC [36], and Lv et al showed that increased LncRNA H19 contributes to migration and invasiveness of HCC cells, which is accompanied by miR-675 downregulation [37]. STAT3 signaling promotes HCC progression through the suppression of apoptosis through the induction of [38].…”

Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma

“…Moreover, their analysis also indicated that by altering the epigenetic activation of miR-200 with cooperation of the protein complex hnRNP U/PCAF/RNA Pol II, H19 could suppress HCC metastasis and cause EMT. Similarly, based on the conclusion of Jun et al [78], H19, working together with miR-675, promotes migration and invasion of HCC through the AKT/GSK-3β/Cdc25A signaling pathway, providing evidence that this type of lncRNA could be a potent diagnostic biomarker and therapeutic target for HCC.…”