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环状BANP通过吸附let-7d-5p调节HMGA1/Wnt/β-连环蛋白信号通路,促进结直肠癌的生长和转移。

circBANP promotes colorectal cancer growth and metastasis via sponging let-7d-5p to modulate HMGA1/Wnt/β-catenin signaling.

作者信息

Ni Yijiang, Lu Chen, Wang Wulin, Gao Wenjie, Yu Chunzhao

机构信息

Department of General Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu Province, P.R. China.

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Changzhou, Nanjing Medical University, Changzhou 213000, Jiangsu Province, P.R. China.

出版信息

Mol Ther Oncolytics. 2021 Mar 23;21:119-133. doi: 10.1016/j.omto.2021.03.012. eCollection 2021 Jun 25.

Abstract

Colorectal cancer (CRC) is one of the most common and deadly cancers, and the incidence of CRC is on the rise. Due to the lack of early diagnosis method and high metastasis of the disease, the prognosis of CRC remains very poor. Exploring the underlying molecular mechanisms of CRC is very necessary for effective therapy. In this study, we investigated the function of circBANP in CRC. The results showed that circBANP was elevated in both CRC tissues and cells and its level positively correlated with the stage of CRC. Knockdown of circBANP greatly suppressed the epithelial-mesenchymal transition (EMT) process and CRC cell proliferation, migration, and invasion. In addition, knockdown of circBANP inhibited CRC tumor growth and metastasis . Further, circBANP directly bound to let-7d-5p and regulated CRC development via acting as a let-7d-5p sponge. Let-7d-5p directly targeted HMGA1 and thus circBANP/let-7d-5p regulated Wnt/β-catenin signaling via HMGA1. Collectively, circBANP promotes CRC development and metastasis via acting as a let-7d-5p sponge to regulate HMGA1/Wnt/β-catenin signaling, providing a potential biomarker and therapeutic target for the management of CRC.

摘要

结直肠癌(CRC)是最常见且致命的癌症之一,并且CRC的发病率正在上升。由于缺乏早期诊断方法以及该疾病的高转移性,CRC的预后仍然非常差。探索CRC潜在的分子机制对于有效治疗非常必要。在本研究中,我们调查了circBANP在CRC中的功能。结果显示,circBANP在CRC组织和细胞中均升高,并且其水平与CRC的分期呈正相关。敲低circBANP极大地抑制了上皮-间质转化(EMT)过程以及CRC细胞的增殖、迁移和侵袭。此外,敲低circBANP抑制了CRC肿瘤的生长和转移。进一步研究发现,circBANP直接与let-7d-5p结合,并通过充当let-7d-5p的海绵来调节CRC的发展。Let-7d-5p直接靶向HMGA1,因此circBANP/let-7d-5p通过HMGA1调节Wnt/β-连环蛋白信号通路。总的来说,circBANP通过充当let-7d-5p的海绵来调节HMGA1/Wnt/β-连环蛋白信号通路,从而促进CRC的发展和转移,为CRC的治疗提供了一个潜在的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76e3/8079336/6904af5f7a54/fx1.jpg

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