SNTB1 regulates colorectal cancer cell proliferation and metastasis through YAP1 and the WNT/β-catenin pathway

ABSTRACTColorectal cancer is a common type of digestive tract cancer with a significant morbidity and death rate across the world, partially attributing to the metastasis-associated problems. In this study, integrative bioinformatics analyses were performed to identify genes that might contribute to colorectal cancer metastasis, and 293 genes were dramatically increased and 369 genes were decreased within colon cancer samples. Among up-regulated genes, top five genes correlated with colorectal cancer patient’s prognosis were verified for expression in clinical samples and syntrophin beta 1 (SNTB1) was the most up-regulated. In vitro, SNTB1 knockdown suppresses the malignant behaviors of colorectal cancer cells, including cell viability, colony formation capacity, as well as the abilities to migrate and invade. Furthermore, SNTB1 knockdown decreased the levels of Wnt1, C-Jun, C-Myc, TCF7, and cyclin D1, and inhibited EMT in both cell lines. In vivo, SNTB1 knockdown inhibited tumor growth and metastasis in nude mice models. SNTB1 positively regulated Yes1 associated transcriptional regulator (YAP1) expression; YAP1 partially reversed the effects of SNTB1 on colorectal cancer cell phenotypes and the Wnt/β-catenin/MYC signaling. In conclusion, SNTB1 knockdown inhibits colorectal cancer cell aggressiveness in vitro and tumor growth and metastasis in vivo through the Wnt/β-catenin/MYC signaling; YAP1 might mediate SNTB1 functions on colorectal cancer.KEYWORDS: Colorectal cancermetastasisSNTB1YAP1the Wnt/β-catenin/MYC signaling Disclosure statementNo potential conflict of interest was reported by the authors.Ethical approvalAll procedures performed in studies involving human participants were in accordance with the ethical standards of Third Xiangya Hospital of Central South University and the 1964 Helsinki declaration. Informed consent to participate in the study has been obtained from participants.The guidelines for the care and use of animals were carried out according to the Ethics Committee’s Guidelines for laboratory animals of Third Xiangya Hospital of Central South University.Consent for publicationConsent for publication was obtained from the participants.Data availability statementThe authors confirm that the data supporting the findings of this study are available within the article.Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2023.2244778Additional informationFundingThis study was supported by the Foundation of China Hunan Provincial Science & Technology Department (2021SK2001), National Key Research and Development Program of China (2022YFE0134700) and the National Natural Science Foundation of China (51875580).