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微小 RNA-329 通过直接靶向转化生长因子-β1 在结直肠癌中发挥肿瘤抑制作用。

MicroRNA‑329 serves a tumor suppressive role in colorectal cancer by directly targeting transforming growth factor beta‑1.

机构信息

Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250033, P.R. China.

Health Management Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.

出版信息

Mol Med Rep. 2017 Oct;16(4):3825-3832. doi: 10.3892/mmr.2017.7077. Epub 2017 Jul 24.

DOI:10.3892/mmr.2017.7077
PMID:29067459
Abstract

Colorectal cancer (CRC) is the third most common type of diagnosed cancer and the fourth leading cause of cancer‑associated mortalities worldwide. Increasing studies have demonstrated that the deregulation of microRNAs (miRNAs or miRs) is associated with the occurrence and development of multiple types of human cancer, including CRC. miR‑329 has been identified to be downregulated in various types of cancer; however, its expression pattern, functions and mechanisms in CRC remain unclear. The present study demonstrated that miR‑329 was lowly expressed in CRC tissue samples and cell lines. Low expression of miR‑329 was correlated with tumor‑node‑metastasis stage and lymph node metastasis in patients with CRC. In vitro experiments revealed that resumption expression of miR‑329 suppressed cell proliferation and invasion in CRC. Furthermore, the results of the present study indicated that miR‑329 targets transforming growth factor‑β1 (TGF‑β1) directly in vitro. TGF‑β1 was demonstrated to be upregulated in CRC tissue samples and inversely correlated with miR‑329 expression. Upregulation of TGF‑β1 was able to partially counteract the antitumor roles of miR‑329 on CRC cell proliferation and invasion. The results of the current study revealed that miR‑329 suppresses CRC cell proliferation and invasion through targeting TGF‑β1, thus suggesting that targeting miR‑329/TGF‑β1 may provide a novel effective therapeutic approach for the treatment of patients with CRC.

摘要

结直肠癌(CRC)是全球第三大常见癌症类型,也是癌症相关死亡的第四大主要原因。越来越多的研究表明,microRNAs(miRNAs 或 miRs)的失调与多种人类癌症的发生和发展有关,包括 CRC。已经发现 miR-329 在多种类型的癌症中下调;然而,其在 CRC 中的表达模式、功能和机制尚不清楚。本研究表明 miR-329 在 CRC 组织样本和细胞系中低表达。miR-329 的低表达与 CRC 患者的肿瘤-淋巴结-转移分期和淋巴结转移相关。体外实验表明,miR-329 的恢复表达抑制了 CRC 中的细胞增殖和侵袭。此外,本研究的结果表明,miR-329 在体外直接靶向转化生长因子-β1(TGF-β1)。CRC 组织样本中 TGF-β1 上调,与 miR-329 表达呈负相关。TGF-β1 的上调能够部分抵消 miR-329 对 CRC 细胞增殖和侵袭的抗肿瘤作用。本研究结果表明,miR-329 通过靶向 TGF-β1 抑制 CRC 细胞的增殖和侵袭,提示靶向 miR-329/TGF-β1 可能为 CRC 患者的治疗提供一种新的有效治疗方法。

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引用本文的文献

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Int J Mol Sci. 2022 Nov 20;23(22):14436. doi: 10.3390/ijms232214436.
2
Construction and prognostic analysis of miRNA-mRNA regulatory network in liver metastasis from colorectal cancer.结直肠癌肝转移中miRNA-mRNA调控网络的构建及预后分析
World J Surg Oncol. 2021 Jan 4;19(1):7. doi: 10.1186/s12957-020-02107-z.
3
miR-4666-3p and miR-329 Synergistically Suppress the Stemness of Colorectal Cancer Cells via Targeting TGF-β/Smad Pathway.
miR-4666-3p和miR-329通过靶向TGF-β/Smad信号通路协同抑制结肠癌细胞的干性
Front Oncol. 2019 Nov 19;9:1251. doi: 10.3389/fonc.2019.01251. eCollection 2019.
4
Role of epigenetics in transformation of inflammation into colorectal cancer.表观遗传学在炎症向结直肠癌转化中的作用。
World J Gastroenterol. 2019 Jun 21;25(23):2863-2877. doi: 10.3748/wjg.v25.i23.2863.