PTOV1 facilitates colorectal cancer cell proliferation through activating AKT1 signaling pathway

Si-An Xie; Wen Zhang; Feng Du; Si Liu; Ting-Ting Ning; Nan Zhang; Shu-Tian Zhang; Sheng-Tao Zhu

Heliyon (Aug 2024)

PTOV1 facilitates colorectal cancer cell proliferation through activating AKT1 signaling pathway

Si-An Xie,
Wen Zhang,
Feng Du,
Si Liu,
Ting-Ting Ning,
Nan Zhang,
Shu-Tian Zhang,
Sheng-Tao Zhu

Affiliations

Si-An Xie: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China; National Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, PR China
Wen Zhang: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China
Feng Du: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China; National Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, PR China
Si Liu: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China; National Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, PR China
Ting-Ting Ning: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China; National Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, PR China
Nan Zhang: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China; National Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, PR China
Shu-Tian Zhang: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China; National Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, PR China; Corresponding author. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China.
Sheng-Tao Zhu: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China; National Key Laboratory of Digestive Health, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, PR China; Corresponding author. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, PR China.

Journal volume & issue: Vol. 10, no. 16
p. e36017

Abstract

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Background: Colorectal 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. Methods: Our 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. Results: Our 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. Conclusion: The 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.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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