Dataset Information

MTP18 overexpression contributes to tumor growth and metastasis and associates with poor survival in hepatocellular carcinoma.

ABSTRACT:

Background

Human MTP18 (mitochondrial protein 18?kDa) is a novel nuclear-encoded mitochondrial membrane protein that is involved in controlling mitochondrial fission. Our bioinformatic analysis of TCGA data revealed an aberrant overexpression of MTP18 in hepatocellular carcinoma (HCC). We analyzed its biological effects and prognostic significance in this malignancy.

Methods

MTP18 expression was evaluated by qRT-PCR and western blot analysis in 20 paired tumor and peritumor tissues. Clinical impact of MTP18 overexpression was assessed in 156 patients with HCC. The effects of MTP18 knockdown or overexpression on cell growth and metastasis were determined by cell proliferation, colony formation, cell cycle, apoptosis, migration, and invasion assays. Furthermore, the underlying molecular mechanisms by which MTP18 overexpression promoted HCC cell growth and metastasis were explored.

Results

MTP18 was commonly overexpressed in HCC tissues mainly due to the downregulation of miR-125b, which significantly contributed to poor prognosis of HCC patients. Functional experiments revealed that MTP18 promoted both the growth and metastasis of HCC cells by inducing the progression of cell cycle, epithelial to mesenchymal transition (EMT) and production of MMP-9, and suppressing cell apoptosis. Mechanistically, increased mitochondrial fission and subsequent ROS production was found to be involved in the promotion of growth and metastasis by MTP18 in HCC cells.

Conclusions

MTP18 plays a pivotal oncogenic role in hepatocellular carcinogenesis; its overexpression may serve as a novel prognostic factor and a therapeutic target in HCC.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6148245 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

MTP18 overexpression contributes to tumor growth and metastasis and associates with poor survival in hepatocellular carcinoma.

Zhang Yu Y Li Hui H Chang Hulin H Du Lixue L Hai Jun J Geng Xilin X Yan Xiang X

Cell death & disease 20180920 10

<h4>Background</h4>Human MTP18 (mitochondrial protein 18 kDa) is a novel nuclear-encoded mitochondrial membrane protein that is involved in controlling mitochondrial fission. Our bioinformatic analysis of TCGA data revealed an aberrant overexpression of MTP18 in hepatocellular carcinoma (HCC). We analyzed its biological effects and prognostic significance in this malignancy.<h4>Methods</h4>MTP18 expression was evaluated by qRT-PCR and western blot analysis in 20 paired tumor and peritumor tissue ...[more]

PMID: 30237394

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Project description:PurposeOur research was aimed to identify the expression, clinical value and biological significance of GINS complex subunit 4 (GINS4) in hepatocellular carcinoma (HCC).Materials and methodsGINS4 was initially screened through weighted gene co-expression network analysis (WGCNA). The TCGA, GEO, and TIMER databases were applied for analyzing the GINS4 mRNA expression in HCC. GINS4 protein levels were detected via immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve was applied for estimating the diagnostic significance of GINS4 in HCC. Kaplan-Meier plots, Cox model, and nomogram were used to assess the prognostic performance of GINS4 in HCC. Nomogram validation was conducted through time-dependent ROC and decision curve analysis (DCA). The Wanderer, UALCAN, and DiseaseMeth databases were utilized to identify GINS4 methylation levels in HCC. Genes co-expressed with GINS4 in HCC were estimated through the TCGA, cBioPortal, and GEPIA. GO, KEGG, and GSEA unraveled the possible biological mechanisms of GINS4 in HCC.ResultsWGCNA confirmed that GINS4 was one of hub genes significantly associated with histological grade of HCC. Multiple databases confirmed the significant upregulation of GINS4 in HCC tissues compared with non-tumor controls. IHC analysis of 35 HCC patients demonstrated that overexpressed GINS4 positively correlated with advanced TNM stage and poor pathological differentiation. GINS4 could effectively differentiate HCC cases from healthy individuals, with an AUC of 0.865. Increased GINS4 expression predicted unsatisfactory prognosis in HCC patients, especially in age >60 years, histological grade 1, HBV infection-negative, and occurring relapse subgroup. Nomogram incorporating GINS4 level and TNM stage displayed satisfactory predictive accuracy and clinical utility in predicting HCC prognosis. Upregulated GINS4 exhibited hypomethylated levels in HCC. Functional analysis indicated that GINS4 potentially positively modulated cell cycle and PI3K/AKT/mTOR pathway.ConclusionGINS4 is overexpressed in HCC and is correlated with undesirable survival of HCC patients.

Dataset Information

MTP18 overexpression contributes to tumor growth and metastasis and associates with poor survival in hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

MTP18 overexpression contributes to tumor growth and metastasis and associates with poor survival in hepatocellular carcinoma.

Similar Datasets

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