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微小 RNA-539 通过直接靶向 IGF-1R 抑制胰腺导管腺癌中的细胞增殖、集落形成和侵袭。

MicroRNA‑539 inhibits cell proliferation, colony formation and invasion in pancreatic ductal adenocarcinoma by directly targeting IGF‑1R.

机构信息

Department of Emergency, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.

Department of General Surgery, The 89th Hospital of Chinese People's Liberation Army, Weifang, Shandong 262500, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):1804-1811. doi: 10.3892/mmr.2018.9109. Epub 2018 May 31.

Abstract

MicroRNAs (miRNAs) possess oncogenic and tumour‑suppressive roles in the carcinogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) by regulating the expression of numerous cancer‑related genes. Thus, the investigation on the expression and roles of miRNAs in PDAC may facilitate the identification of novel and effective targets for the clinical diagnosis and treatment of patients with PDAC. miRNA‑539 (miR‑539) has been studied in multiple types of human cancer. However, its expression and potential biological function in PDAC remain unclear. In the current study, the expression level, clinical significance, roles and underlying molecular mechanism of miR‑539 in PDAC. The present results demonstrated that miR‑539 expression was downregulated in PDAC tissues and cell lines. A low miR‑539 level was associated with TNM stage and lymph node metastasis of patients with PDAC. miR‑539 overexpression induced a significant reduction in the proliferation, colony formation and invasion of PDAC cells. Insulin‑like growth factor 1 receptor (IGF‑1R) was confirmed as a direct target gene of miR‑539 in PDAC. Further analysis indicated that IGF‑1R was overexpressed in PDAC tissues. Notably, the mRNA expression of IGF‑1R was negatively correlated with miR‑539 levels in PDAC tissues. In addition, the recovered IGF‑1R expression also partially counteracted the suppressive roles of miR‑539 overexpression in PDAC cells. Overall, miR‑539 may inhibit the aggressive behaviour of PDAC by directly targeting IGF‑1R and may serve as a novel therapeutic target for patients with this disease.

摘要

微小 RNA(miRNAs)通过调节众多癌症相关基因的表达,在胰腺导管腺癌(PDAC)的发生和进展中具有致癌和抑癌作用。因此,研究 miRNAs 在 PDAC 中的表达和作用可能有助于为 PDAC 患者的临床诊断和治疗确定新的有效靶点。miR-539(miR-539)在多种人类癌症中都有研究。然而,其在 PDAC 中的表达和潜在生物学功能尚不清楚。在本研究中,研究了 miR-539 在 PDAC 中的表达水平、临床意义、作用及其潜在的分子机制。目前的结果表明,miR-539 在 PDAC 组织和细胞系中的表达水平下调。miR-539 水平低与 PDAC 患者的 TNM 分期和淋巴结转移相关。miR-539 过表达可显著抑制 PDAC 细胞的增殖、集落形成和侵袭。胰岛素样生长因子 1 受体(IGF-1R)被证实为 PDAC 中 miR-539 的直接靶基因。进一步分析表明,IGF-1R 在 PDAC 组织中过度表达。值得注意的是,IGF-1R 的 mRNA 表达与 PDAC 组织中 miR-539 水平呈负相关。此外,恢复 IGF-1R 的表达也部分抵消了 miR-539 过表达对 PDAC 细胞的抑制作用。总之,miR-539 可能通过直接靶向 IGF-1R 抑制 PDAC 的侵袭行为,可能成为该疾病患者的一种新的治疗靶点。

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