miR-25-3p 通过调控泛素连接酶 FBXW7 的功能在结直肠癌细胞中发挥致癌作用。

miR‑25‑3p serves as an oncogenic in colorectal cancer cells by regulating the ubiquitin ligase FBXW7 function.

机构信息

General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China.

出版信息

Oncol Rep. 2024 Nov;52(5). doi: 10.3892/or.2024.8812. Epub 2024 Sep 27.

Abstract

Accumulating evidence indicates that the dysregulation of microRNAs (miRNAs or miRs), is associated with human malignancies and suggests a casual role of miRNAs in tumor initiation and progression. Even though it has been discovered that a number of miRNAs play significant parts in the development of colorectal cancer (CRC), it is crucial to comprehend the regulatory functions that other miRNAs play in CRC. Based on GSE183437 and GSE156719 microarray data that were obtained from Gene Expression Omnibus database, candidate miRNAs were researched. The oncogenic effects of miR‑25‑3p in different malignancies have led to its selection for additional investigation in the present study. The expression of miR‑25‑3p was verified by reverse transcription‑quantitative PCR, and its correlation with clinicopathological characteristics in patients with CRC was then investigated. assays were conducted to investigate the influence of miR‑25‑3p on the proliferative and apoptotic behaviors of HCT116 and Caco‑2 cells. The present data revealed that miR‑25‑3p exhibited one of the most significant upregulations in CRC tissues and cell lines. The expression levels of miR‑25‑3p were found to be intimately correlated with tumor size, distant metastasis, tumor‑node‑metastasis stage, and shorter overall survival rate. In terms of functionality, the downregulation of miR‑25‑3p led to the inhibition of cellular proliferation and the enhancement of apoptosis in both HCT116 and Caco‑2 cell lines. The critical tumor suppressor F‑box and WD repeat containing domain 7 (FBXW7) was identified as a direct molecular target for miR‑25‑3p, with an inverse relationship observed between the two in neoplastic tissues. Subsequent studies demonstrated that the tumor suppressive effects of miR‑25‑3p inhibitor were effectively negated by the silencing of FBXW7. Moreover, the ability of FBXW7 to inhibit the expression of several oncogenes was deemed essential for countering the anticancer effects mediated by miR‑25‑3p downregulation. These findings posit miR‑25‑3p as a promising therapeutic target and prognostic indicator for CRC.

摘要

越来越多的证据表明,微小 RNA(miRNAs 或 miR)的失调与人类恶性肿瘤有关,并表明 miRNAs 在肿瘤发生和发展中起着因果作用。尽管已经发现许多 miRNAs 在结直肠癌(CRC)的发展中起着重要作用,但了解其他 miRNAs 在 CRC 中发挥的调节功能至关重要。本研究基于从基因表达综合数据库(Gene Expression Omnibus database)获得的 GSE183437 和 GSE156719 微阵列数据,研究了候选 miRNAs。miR-25-3p 在不同恶性肿瘤中的致癌作用促使其在本研究中进一步研究。通过逆转录-定量 PCR 验证 miR-25-3p 的表达,并随后研究其与 CRC 患者临床病理特征的相关性。进行了实验以研究 miR-25-3p 对 HCT116 和 Caco-2 细胞增殖和凋亡行为的影响。本研究数据显示,miR-25-3p 在 CRC 组织和细胞系中表现出最显著的上调之一。miR-25-3p 的表达水平与肿瘤大小、远处转移、肿瘤-淋巴结-转移分期以及较短的总生存率密切相关。在功能方面,下调 miR-25-3p 导致 HCT116 和 Caco-2 细胞系中细胞增殖受到抑制,凋亡增强。关键的肿瘤抑制因子 F-box 和 WD 重复结构域 7(FBXW7)被鉴定为 miR-25-3p 的直接分子靶标,两者在肿瘤组织中呈负相关。随后的研究表明,miR-25-3p 抑制剂的肿瘤抑制作用可通过 FBXW7 的沉默有效消除。此外,FBXW7 抑制几种癌基因的表达对于抵消 miR-25-3p 下调介导的抗癌作用至关重要。这些发现将 miR-25-3p 作为 CRC 的一种有前途的治疗靶点和预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e051/11450686/d38ac1f6c5a4/or-52-05-08812-g00.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索