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miR-130a-3p 通过靶向 Wnt 家族成员 1(WNT1)抑制结直肠癌生长。

MiR-130a-3p suppresses colorectal cancer growth by targeting Wnt Family Member 1 (WNT1).

机构信息

Department of Oncology, People's Hospital of Yuechi County, Yuechi County, Sichuan Province, China.

Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.

出版信息

Bioengineered. 2021 Dec;12(1):8407-8418. doi: 10.1080/21655979.2021.1977556.

Abstract

The microRNA miR-130a-3p (miR-130a-3p) has anti-tumor activity against numerous cancer types. Further, miR-130a-3p may target Wnt signaling, which is a critical pathway regulating tumorigenesis. Functions of miR-130a-3p in colorectal cancer (CRC) and contributions of Wnt1 pathway modulation, however, have not been examined, hence the exploration on these two aspects. In this study, in comparison with normal controls, both CRC tissue and multiple CRC cell lines showed downregulated miR-130a-3p. MiR-130a-3p overexpression contributed to a decrease in CRC cell proliferation. Additionally, its overexpression also caused reduced expression of WNT Family Member 1 (WNT1) and downstream WNT pathway factors c-myc and cyclin D1. Dual-luciferase assay revealed WNT1 as a direct target of miR-130a-3p, and further the inhibitory effect of miR-130a-3p on c-myc and cyclin D1 was proved to be reversed by overexpressed WNT1. Collectively, miR-130a-3p inhibits CRC growth by directly targeting WNT1, and miR-130a-3p and WNT1 pathway-associated factors are defined as potential targets for CRC treatment.

摘要

微小 RNA miR-130a-3p(miR-130a-3p)对多种癌症具有抗肿瘤活性。此外,miR-130a-3p 可能靶向 Wnt 信号通路,该通路是调节肿瘤发生的关键途径。然而,miR-130a-3p 在结直肠癌(CRC)中的功能及其对 Wnt1 通路调节的贡献尚未得到检验,因此对这两个方面进行了探索。在这项研究中,与正常对照组相比,CRC 组织和多种 CRC 细胞系均显示 miR-130a-3p 下调。miR-130a-3p 的过表达导致 CRC 细胞增殖减少。此外,其过表达还导致 WNT 家族成员 1(WNT1)和下游 WNT 通路因子 c-myc 和细胞周期蛋白 D1 的表达降低。双荧光素酶报告基因实验显示 WNT1 是 miR-130a-3p 的直接靶基因,并且进一步证明 miR-130a-3p 对 c-myc 和细胞周期蛋白 D1 的抑制作用可被过表达的 WNT1 逆转。综上所述,miR-130a-3p 通过直接靶向 WNT1 抑制 CRC 生长,miR-130a-3p 和 WNT1 通路相关因子被定义为 CRC 治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eec/8806712/b0013d89a273/KBIE_A_1977556_F0001_OC.jpg

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