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Down-Regulating HAUS6 Suppresses Cell Proliferation by Activating the p53/p21 Pathway in Colorectal Cancer.

ABSTRACT: Background: HAUS6 participates in microtubule-dependent microtubule amplification, but its role in malignancies including colorectal cancer (CRC) has not been explored. We therefore assessed the potential oncogenic activities of HAUS6 in CRC. Results: HAUS6 mRNA and protein expression is higher in CRC tissues, and high HAUS6 expression is correlated with shorter overall survival in CRC patients. HAUS6 knockdown in CRC cell lines suppressed cell growth in vitro and in vivo by inhibiting cell viability, survival and arresting cell cycle progression at G0/G1, while HAUS6 over-expression increased cell viability. We showed that these effects are dependent on activation of the p53/p21 signalling pathway by reducing p53 and p21 degradation. Moreover, combination of HAUS6 knockdown and 5-FU treatment further enhanced the suppression of cell proliferation of CRC cells by increasing activation of the p53/p21 pathway. Conclusion: Our study highlights a potential oncogenic role for HAUS6 in CRC. Targeting HAUS6 may be a promising novel prognostic marker and chemotherapeutic target for treating CRC patients.

SUBMITTER: Shen A

PROVIDER: S-EPMC8790508 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Down-Regulating HAUS6 Suppresses Cell Proliferation by Activating the p53/p21 Pathway in Colorectal Cancer.

Shen Aling A Liu Liya L Huang Yue Y Shen Zhiqing Z Wu Meizhu M Chen Xiaoping X Wu Xiangyan X Lin Xiaoying X Chen Youqin Y Li Li L Cheng Ying Y Chu Jianfeng J Sferra Thomas J TJ Wei Lihui L Zhuang Qunchuan Q Peng Jun J

Frontiers in cell and developmental biology 20220112

Background: HAUS6 participates in microtubule-dependent microtubule amplification, but its role in malignancies including colorectal cancer (CRC) has not been explored. We therefore assessed the potential oncogenic activities of HAUS6 in CRC. Results: HAUS6 mRNA and protein expression is higher in CRC tissues, and high HAUS6 expression is correlated with shorter overall survival in CRC patients. HAUS6 knockdown in CRC cell lines suppressed cell growth in vitro and in vivo ...[more]

PMID: 35096810

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Project description:BackgroundColorectal cancer is a predominant contributor to global cancer-related morbidity and mortality. The oncogene PTOV1 has been linked to various human malignancies, yet its specific role in CRC pathogenesis requires further elucidation.MethodsOur study used a comprehensive array of authoritative bioinformatics tools, such as TIMER, UCSC Xena, GEO, Human Protein Atlas, UALCAN, CIBERSORTx and others which used to investigate the complex effects of PTOV1 on gene expression profiles, diagnostic and prognostic biomarkers, tumor immunology, signaling pathways, epigenetic alterations, and genetic mutations. Gene expression validation was conducted using Western blot and qRT-PCR. The in vitro proliferative and migratory potentials of CRC cells were evaluated using CCK-8 assays, colony formation, and transwell migration assays, respectively. MSP was applied to assess the methylation status of the PTOV1 promoter region.ResultsOur results reveal a significant association between increased PTOV1 expression, driven by promoter hypomethylation, and poor patient prognosis in CRC. Elevated PTOV1 levels were positively correlated with the enrichment of diverse immune cell subsets and immune-related molecules within the tumor microenvironment. In vitro assays demonstrated that PTOV1 knockdown markedly reduced CRC cell proliferation, colony formation, and migration, while ectopic PTOV1 expression had the opposite effect. Importantly, PTOV1 was shown to regulate the PI3K-AKT signaling pathway, significantly influencing the phosphorylation of AKT1 and the expression of cell cycle regulators P21 and P27. The pharmacological inhibition of AKT1 phosphorylation using MK2206 effectively counteracted the proliferative effects induced by PTOV1 overexpression.ConclusionThe ability of PTOV1 to enhance CRC cell proliferation via modulation of the AKT1 signaling pathway establishes it as a potential therapeutic target and a promising biomarker for prognostic stratification in CRC.

Dataset Information

Down-Regulating HAUS6 Suppresses Cell Proliferation by Activating the p53/p21 Pathway in Colorectal Cancer.

Publications

Down-Regulating HAUS6 Suppresses Cell Proliferation by Activating the p53/p21 Pathway in Colorectal Cancer.

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