MAPKAPK5-AS1 drives the progression of hepatocellular carcinoma via regulating miR-429/ZEB1 axis.

Hepatocellular carcinoma (HCC) is a common malignancy. Long non-coding RNAs (lncRNAs) partake in the progression of HCC. However, the role of lncRNA MAPKAPK5-AS1 in the development of HCC has not been fully clarified. RNA sequencing data and quantitative real-time polymerase chain reaction (qRT-PCR) were adopted to analyze MAPKAPK5-AS1, miR-429 and ZEB1 mRNA expressions in HCC tissues and cell lines. Western blot was used to detect ZEB1, E-cadherin and N-cadherin protein expressions. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and flow cytometry assays were adopted to analyze the effects of MAPKAPK5-AS1 on cell proliferation, migration, invasion and apoptosis. Besides, luciferase reporter assay was used to detect the targeting relationship between miR-429 and MAPKAPK5-AS1 or ZEB1 3'UTR. The xenograft tumor mouse models were used to explore the effect of MAPKAPK5-AS1 on lung metastasis of HCC cells. MAPKAPK5-AS1 and ZEB1 expressions were up-regulated in HCC tissues, and miR-429 expression is down-regulated in HCC tissues. MAPKAPK5-AS1 knockdown could significantly impede HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), as well as promote cell apoptosis. MAPKAPK5-AS1 overexpression could enhance L02 cell proliferation, migration, invasion and EMT, and inhibit cell apoptosis. MiR-429 was validated to be the target of MAPKAPK5-AS1, and miR-429 inhibitors could partially offset the effects of knocking down MAPKAPK5-AS1 on HCC cells. MAPKAPK5-AS1 could positively regulate ZEB1 expression through repressing miR-429. Moreover, fewer lung metastatic nodules were observed in the lung tissues of nude mice when the MAPKAPK5-AS1 was knocked down in HCC cells. MAPKAPK5-AS1 can adsorb miR-429 to promote ZEB1 expression to participate in the development of HCC.

Peng Z ，Ouyang X ，Wang Y ，Fan Q ... -  《BMC Molecular and Cell Biology》

Long non-coding RNA MAPKAPK5-AS1/PLAGL2/HIF-1α signaling loop promotes hepatocellular carcinoma progression.

Wang L ，Sun L ，Liu R ，Mo H ，Niu Y ，Chen T ，Wang Y ，Han S ，Tu K ，Liu Q ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

LncRNA ZEB1-AS1 regulates hepatocellular carcinoma progression by targeting miR-23c.

Xue S ，Lu F ，Sun C ，Zhao J ，Zhen H ，Li X ... -  《World Journal of Surgical Oncology》

Long non-coding RNA TTN antisense RNA 1 facilitates hepatocellular carcinoma progression via regulating miR-139-5p/SPOCK1 axis.

Zhu X ，Jiang S ，Wu Z ，Liu T ，Zhang W ，Wu L ，Xu L ，Shao M ... -  《-》

Long non-coding RNA ZEB1-AS1 promotes proliferation and metastasis of hepatocellular carcinoma cells by targeting miR-299-3p/E2F1 axis.

There is emerging evidence that dysregulation of long non-coding RNAs (lncRNAs) is associated with hepatocellular carcinoma (HCC). Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) functions as an oncogenic regulator in various malignancies. Nonetheless, the potential role of ZEB1-AS1 in HCC remains poorly elucidated. Herein, qRT-PCR was employed for examining ZEB1-AS1, miR-299-3p and E2F transcription factor 1 (E2F1) mRNA expressions in HCC cells and tissues. MTT assay was performed to evaluate cell proliferation. Transwell assay was utilized for evaluating cancer cell migration and invasion. Western blot was employed for measuring E2F1 protein expression. What's more, dual-luciferase reporter assay was utilized for verifying the targeting relationships between ZEB1-AS1 and miR-299-3p, as well as E2F1 and miR-299-3p. It was demonstrated that, in HCC tissues and cells, ZEB1-AS1 expression was markedly increased, and meanwhile, its high expression level is related to the unfavourable clinicopathologic indicators. ZEB1-AS1 overexpression facilitated HCC cell proliferation, migration and invasion, while its knockdown led to the opposite effects. In terms of mechanism, we discovered that ZEB1-AS1 could decoy miR-299-3p and upregulate E2F1 expression. This work reveals the functions and mechanism of ZEB1-AS1 in HCC tumourigenesis and progression, which provides novel biomarkers and therapeutic targets for HCC.

Mu B ，Lv C ，Liu Q ，Yang H ... -  《-》