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Long noncoding RNA DUXAP8 contributes to the progression of hepatocellular carcinoma via regulating miR-422a/PDK2 axis.

ABSTRACT: BACKGROUND:Hepatocellular carcinoma (HCC) is one of the most deadly cancer worldwide. Multiple long noncoding RNAs (lncRNAs) are recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the functon and mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in the progression of HCC. METHODS:Expression levels of DUXAP8 in HCC tissue samples were measured using qRT-PCR. The association between pathological indexes and the expression of DUXAP8 was also analyzed. Human HCC cell lines SMMC-7721 and QSG-7701 were used in in vitro studies. CCK-8 assay was used to assess the effect of DUXAP8 on HCC cell line proliferation. Scratch healing assay and Transwell assay were conducted to detect the effect of DUXAP8 on migration and invasion. Furthermore, dual-luciferase reporter assay was used to confirm targeting relationship between miR-422a and DUXAP8. Additionally, Western blot was used to detect the regulatory function of DUXAP8 on pyruvate dehydrogenase kinase 2 (PDK2). RESULTS:DUXAP8 expression HCC clinical samples was significantly increased and this was correlated with unfavorable pathological indexes. High expression of DUXAP8 was associated with shorter overall survival time of patients. Its overexpression remarkably facilitated the proliferation, metastasis, and epithelial-mesenchymal transition of HCC cells. Accordingly, knockdown of it suppressed the malignant phenotypes of HCC cells. Overexpression of DUXAP8 significantly reduced the expression of miR-422a by sponging it, but enhanced the expression of PDK2. CONCLUSIONS:DUXAP8 was a sponge of tumor suppressor miR-422a in HCC, enhanced the expression of PDK2 indirectly, and functioned as an oncogenic lncRNA.

SUBMITTER: Wei F

PROVIDER: S-EPMC7131864 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Long noncoding RNA DUXAP8 contributes to the progression of hepatocellular carcinoma via regulating miR-422a/PDK2 axis.

Wei Feifei F Yang Liang L Jiang Dandan D Pan Min M Tang Guiyan G Huang Mingyue M Zhang Jing J

Cancer medicine 20200205 7

<h4>Background</h4>Hepatocellular carcinoma (HCC) is one of the most deadly cancer worldwide. Multiple long noncoding RNAs (lncRNAs) are recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the functon and mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in the progression of HCC.<h4>Methods</h4>Expression levels of DUXAP8 in HCC tissue samples were measured using qRT-PCR. The association between pathological indexes and the expression of D ...[more]

PMID: 32022476

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Project description:A growing number of studies have shown that competitive endogenous RNA (ceRNA) regulatory networks might play important roles during the process of hepatocellular carcinoma (HCC). This study assessed the role of the ceRNA network in immune cell infiltration in HCC. Immune-related gene sets were downloaded from Molecular Signatures Database, and differentially expressed genes were screened based on TCGA HCC transcriptome data. The corresponding miRNAs with low expression and good prognostic implications, and the corresponding lncRNAs with high expression and poor prognostic were identified to construct ceRNA networks. The networks were utilized for clinical correlation analysis and risk model construction, and the CIBERSORT algorithm was applied to assess immune cell infiltration. In this study, the mRNA-miRNA-lncRNA model was used to construct a ceRNA network in HCC using immune-related differentially expressed mRNAs. Assessment of the MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA network axis in HCC showed that a high risk/poor prognosis was significantly correlated with tumor stage and invasion depth. MMP9 was positively correlated with resting M0 macrophages and NK cells and negatively correlated with activated mast cells, resting mast cells, monocytes and activated NK cells. DUXAP8 was positively correlated with M2 macrophages and negatively correlated with MIR4435-2HG, which was positively correlated with M2 macrophages and negatively correlated with activated mast cells, CD8 T cells and follicular helper T cells. The correlation of the MIR4435-2HG/hsa-miR-1-3p/MMP9/hsa-miR-29-3p/DUXAP8 ceRNA network axis with immune cell infiltration provides further information on the mechanism of HCC development. The result might improve our understanding the interactions between immune related genes and non-coding RNAs in the occurrence and development of HCC, and the relevant RNAs might be used as diagnostic and prognostic biomarkers and molecular targets in HCC patients.

Dataset Information

Long noncoding RNA DUXAP8 contributes to the progression of hepatocellular carcinoma via regulating miR-422a/PDK2 axis.

Publications

Long noncoding RNA DUXAP8 contributes to the progression of hepatocellular carcinoma via regulating miR-422a/PDK2 axis.

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