Dataset Information

ATOH8 overexpression inhibits the tumor progression and monocyte chemotaxis in hepatocellular carcinoma.

ABSTRACT: OBJECTIVE:ATOH8 is reported to be associated with the progression of many tumors; however, there are remaining controversies. The aim of this study is to explore the role of ATOH8 in hepatocellular carcinoma (HCC) and its effect on monocyte chemotaxis. METHODS:Bioinformatics analysis was performed based on the LIHC data in GEPIA and LinkedOmic. Fresh human liver cancer and adjacent nontumor tissue specimens were collected at the Shanghai Public Health Clinical Center. qRT-PCR was performed to determine the transcript level, and western blot analysis and ELISA were used to detect protein expression. CCK8, colony formation, wound-healing, Transwell migration and invasion assays were performed to examine cell proliferation, migration and invasion. An HCC xenograft mouse model was used to determine oncogenicity in vivo. Cell apoptosis and related markers were detected by flow cytometry. Additionally, chemotaxis was assessed by the Transwell migration assay. RESULTS:ATOH8 expression is downregulated in HCC tissue and hepatoma cell lines. High expression of ATOH8 predicts a favorable prognosis. Overexpression of ATOH8 in liver cancer cells inhibits proliferation, migration and invasion in vitro, and tumor progression in nude mice. Knockdown of ATOH8 promotes proliferation of Huh7 and EMT-related proteins. Overexpression of ATOH8 increases chemosensitivity to 5-FU, which is probably caused by inhibiting the phosphorylation of AKT (Ser473). Furthermore, overexpression of ATOH8 in Huh7 reduced MCP1 to inhibit chemotactic THP-1, and promoted antitumor inflammatory cytokine (TNF-? and IFN-?) secretion in monocytes. CONCLUSION:In addition to the intrinsic oncosuppressive function of ATOH8 in the liver, ATOH8 may modulate the microenvironment to create an immune activation state. This may partly be attributed to ATOH8 inhibition of the monocyte recruitment via suppressing MCP1 expression so as to promote antitumor inflammatory cytokine secretion in monocytes.

SUBMITTER: Chen L

PROVIDER: S-EPMC7642694 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ATOH8 overexpression inhibits the tumor progression and monocyte chemotaxis in hepatocellular carcinoma.

Chen Liping L Yang Jingmao J Wang Yajie Y Wu Nana N Li Xian X Li Jun J Huang Yangqing Y Cheng Jilin J

International journal of clinical and experimental pathology 20201001 10

<h4>Objective</h4>ATOH8 is reported to be associated with the progression of many tumors; however, there are remaining controversies. The aim of this study is to explore the role of ATOH8 in hepatocellular carcinoma (HCC) and its effect on monocyte chemotaxis.<h4>Methods</h4>Bioinformatics analysis was performed based on the LIHC data in GEPIA and LinkedOmic. Fresh human liver cancer and adjacent nontumor tissue specimens were collected at the Shanghai Public Health Clinical Center. qRT-PCR was ...[more]

PMID: 33165366

Similar Datasets

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.

Project description:Background: Bromodomain-containing protein 7 (BRD7) is identified as a transcriptional regulator and plays an important role in the development and progression of various tumors. Our previous study demonstrated that BRD7 acts as a potential tumor suppressor in hepatocellular carcinoma (HCC). However, the specific molecular mechanism underlying the BRD7-mediated inhibition of HCC progression remains poorly understood. Methods: We performed ChIP-seq analysis to investigate the gene network mediated by BRD7. Immunohistochemical analysis was performed to analyze potential associations between the p53 and BRD7 expression and the effect of their overexpression on disease pathogenesis and outcome. In addition, we performed biological function experiments to determine the effect of BRD7 and p53 on these functions that are central to tumorigenesis. Finally, we employed a BALB/c model for execution of xenograft transplants to examine the effect of either overexpressing or under-expressing BRD7 and p53 on tumor growth in mice injected with cells. Results: Our results suggested that BRD7 regulates the p53 pathway. Specifically, BRD7 was demonstrated to upregulate the transcription level of p53 by directly binding to the upstream regulatory region of the p53 transcriptional initiation site, thereby enhancing its promoter activity. Moreover, immunohistochemical analysis showed that wild-type p53 (WTp53) expression is positively associated with BRD7 expression and survival of patients with HCC. Additionally,changes of p53 expression could affect the tumor suppressive role of BRD7 on HCC cell proliferation, migration/invasion, cell-cycle, and tumor growth in vitro and in vivo. Furthermore, changes of BRD7 expression in HCC cells significantly altered the expression of p53 signal-related molecules such as p21, Bax, Bcl2, and cyclin D1, indicating that BRD7 may positively regulate activation of the p53 pathway. Conclusions: Collectively, our results indicated that BRD7 exerts anti-tumor effects in HCC through transcriptionally activating p53 pathway. These critical roles of BRD7may provide some promising diagnostic and therapeutic targets for HCC.

Dataset Information

ATOH8 overexpression inhibits the tumor progression and monocyte chemotaxis in hepatocellular carcinoma.

Publications

ATOH8 overexpression inhibits the tumor progression and monocyte chemotaxis in hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets