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微小 RNA-130a 在结直肠癌中上调,并通过直接靶向叉头框 F2 促进细胞生长和迁移。

MicroRNA-130a is upregulated in colorectal cancer and promotes cell growth and motility by directly targeting forkhead box F2.

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

Department of Gastrointestinal Surgery, Yinzhou Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315040, P.R. China.

出版信息

Mol Med Rep. 2017 Oct;16(4):5241-5248. doi: 10.3892/mmr.2017.7257. Epub 2017 Aug 16.

Abstract

Colorectal cancer (CRC) is one of the most prevalent cancers among males and females worldwide. Despite progress in diagnostic and therapeutic strategies for CRC patients, the prognosis for patients with advanced CRC remains poor. MicroRNAs (miRNAs/miRs) are a class of highly conserved short, endogenously expressed and single‑stranded non‑coding RNAs. In recent years, increasing studies have demonstrated that dysregulation of miRNAs is closely associated with CRC carcinogenesis and progression. The aim of the present study was to explore the expression, roles and underlying molecular mechanism of miR‑130a in CRC. The results indicated that miR‑130a was significantly upregulated in CRC, and that miR‑130a expression levels were correlated with TNM stage and lymph node metastasis of CRC. Inhibition of miR‑130a markedly suppressed colorectal cancer cell proliferation, migration and invasion. Furthermore, forkhead box F2 (FOXF2) was identified as a direct downstream target gene of miR‑130a in colorectal cancer. Downregulation of FOXF2 could partially reverse the functions induced by miR‑130a under‑expression in CRC cells. These findings suggested that miR‑130a can regulate FOXF2 and function as an oncogene in CRC. Therefore, miR‑130a may serve as a useful therapeutic agent for miRNA‑based CRC targeted therapy.

摘要

结直肠癌(CRC)是全世界男性和女性中最常见的癌症之一。尽管在 CRC 患者的诊断和治疗策略方面取得了进展,但晚期 CRC 患者的预后仍然很差。微小 RNA(miRNA/miRs)是一类高度保守的短、内源性表达和单链非编码 RNA。近年来,越来越多的研究表明,miRNA 的失调与 CRC 的发生和发展密切相关。本研究旨在探讨 miR-130a 在 CRC 中的表达、作用及其潜在的分子机制。结果表明,miR-130a 在 CRC 中显著上调,并且 miR-130a 的表达水平与 CRC 的 TNM 分期和淋巴结转移相关。抑制 miR-130a 可显著抑制结直肠癌细胞的增殖、迁移和侵袭。此外,叉头框 F2(FOXF2)被鉴定为结直肠癌细胞中 miR-130a 的直接下游靶基因。下调 FOXF2 可部分逆转 CRC 细胞中 miR-130a 低表达诱导的功能。这些发现表明,miR-130a 可以调节 FOXF2 并在 CRC 中作为癌基因发挥作用。因此,miR-130a 可能作为基于 miRNA 的 CRC 靶向治疗的有用治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d48/5647080/8fae58c3c055/MMR-16-04-5241-g00.jpg

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