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microRNA-125a 通过靶向 Smurf1 抑制结直肠癌的肿瘤发生。

MicroRNA-125a inhibits tumorigenesis by targeting Smurf1 in colorectal carcinoma.

机构信息

Department of Gastrointestinal Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Cardiology, The No. 1 Hospital of Shijiazhuang, China.

出版信息

FEBS Open Bio. 2019 Jul;9(7):1305-1314. doi: 10.1002/2211-5463.12680. Epub 2019 Jun 17.

Abstract

Aberrant expression of microRNAs (miRNAs) may contribute to the initiation and development of multiple types of human cancer. Several miRNAs have been found to be strongly correlated with the diagnosis, progression, and prognosis of colorectal carcinoma (CRC), but the role of miR-125a in CRC remains unclear. In the present study, the function of miR-125a on the expression of Smad ubiquitin regulatory factor 1 (Smurf1) was investigated in vitro and in vivo. We verified that Smurf1 is a downstream target gene of miR-125a and is involved in miR-125a-mediated regulation of CT26 cell (colon cancer cell) proliferation and migration. Overexpression of miR-125a suppresses CT26 cell growth by inhibiting cell proliferation. Additionally, wound healing assays were performed to show that overexpression of miR-125a significantly reduced CT26 cell migration, which was reversed by overexpression of Smurf1. In vivo, miR-125a overexpression downregulated the expression of Ki67 and Smurf1, thus leading to a marked reduction in tumor growth. These results revealed that miR-125a plays a critical role in CRC by directly targeting Smurf1, a finding that may facilitate the development of improved diagnostic and therapeutic techniques for CRC.

摘要

异常表达的 microRNAs(miRNAs)可能导致多种类型的人类癌症的发生和发展。已经发现一些 miRNAs 与结直肠癌(CRC)的诊断、进展和预后密切相关,但 miR-125a 在 CRC 中的作用仍不清楚。在本研究中,研究人员在体外和体内研究了 miR-125a 对 Smad 泛素调节因子 1(Smurf1)表达的影响。结果验证了 Smurf1 是 miR-125a 的下游靶基因,并参与了 miR-125a 对 CT26 细胞(结肠癌细胞)增殖和迁移的调节。miR-125a 的过表达通过抑制细胞增殖抑制 CT26 细胞的生长。此外,进行了划痕愈合实验以表明 miR-125a 的过表达显著降低 CT26 细胞的迁移,而过表达 Smurf1 则逆转了这种作用。在体内,miR-125a 的过表达下调了 Ki67 和 Smurf1 的表达,从而导致肿瘤生长明显减少。这些结果表明,miR-125a 通过直接靶向 Smurf1 在 CRC 中发挥关键作用,这一发现可能有助于开发用于 CRC 的改进的诊断和治疗技术。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70e3/6609577/41972f1c746c/FEB4-9-1305-g001.jpg

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