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SNTB1 通过 YAP1 和 WNT/β-catenin 通路调节结直肠癌细胞的增殖和转移。

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

机构信息

Department of Gastrointestinal Surgery, the Third Xiangya Hospital, Central South University, Changsha, China.

Department of Nephrology, the Third Xiangya Hospital, Central South University, Changsha, China.

出版信息

Cell Cycle. 2023 Sep;22(17):1865-1883. doi: 10.1080/15384101.2023.2244778. Epub 2023 Aug 17.

Abstract

Colorectal 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. , 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. , 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 and tumor growth and metastasis through the Wnt/β-catenin/MYC signaling; YAP1 might mediate SNTB1 functions on colorectal cancer.

摘要

结直肠癌是一种常见的消化道癌症,在全球范围内具有较高的发病率和死亡率,部分原因是与转移相关的问题。在这项研究中,我们进行了综合的生物信息学分析,以鉴定可能导致结直肠癌转移的基因,结果发现结肠癌样本中 293 个基因显著上调,369 个基因下调。在上调的基因中,我们对与结直肠癌患者预后相关的前 5 个基因进行了临床样本表达验证,结果发现突触结合蛋白β 1(SNTB1)表达上调最为显著。SNTB1 敲低抑制结直肠癌细胞的恶性行为,包括细胞活力、集落形成能力以及迁移和侵袭能力。此外,SNTB1 敲低降低了 Wnt1、C-Jun、C-Myc、TCF7 和 cyclin D1 的水平,并抑制了两种细胞系中的 EMT。SNTB1 敲低抑制裸鼠模型中的肿瘤生长和转移。SNTB1 正向调节 Yes1 相关转录调节剂(YAP1)的表达;YAP1 部分逆转了 SNTB1 对结直肠癌细胞表型和 Wnt/β-catenin/MYC 信号的影响。总之,SNTB1 敲低通过 Wnt/β-catenin/MYC 信号抑制结直肠癌细胞的侵袭性和肿瘤生长转移;YAP1 可能介导 SNTB1 在结直肠癌中的功能。

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