微小 RNA-30c 通过靶向孪生蛋白 1 抑制胰腺癌细胞增殖并提示预后不良。

MicroRNA-30c inhibits pancreatic cancer cell proliferation by targeting twinfilin 1 and indicates a poor prognosis.

机构信息

Department of Ultrasonography, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China.

Department of Information, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China.

出版信息

World J Gastroenterol. 2019 Nov 14;25(42):6311-6321. doi: 10.3748/wjg.v25.i42.6311.

BACKGROUND

Studies have reported that microRNA-30c (miR-30c) has vital functions in the development and progression of multiple cancers.

AIM

To investigate the clinical significance and role of miR-30c in pancreatic cancer.

METHODS

MiR-30c and twinfilin 1 (TWF1) expression levels were analyzed in Gene Expression Omnibus datasets and validated in human pancreatic cancer by quantitative real-time polymerase chain reaction (RT-qPCR). The effects of miR-30c on pancreatic cancer cell growth, apoptosis, and cell cycle were evaluated by CCK-8 and flow cytometry assays. Furthermore, the effects were investigated using a subcutaneous xenograft experiment. Target gene prediction software and luciferase reporter assays were used to identify TWF1 as a direct target of miR-30c.

RESULTS

The expression of miR-30c was significantly decreased in pancreatic cancer tissues and associated with survival. Gain- and loss-of-function assays showed that miR-30c suppressed pancreatic cancer cell proliferation and . RT-qPCR, Western blot, and luciferase reporter assays showed that miR-30c directly targeted TWF1. The expression level of miR-30c was negatively correlated with TWF1 expression in pancreatic cancer tissues. Furthermore, the effects of ectopic miR-30c were rescued by TWF1 overexpression.

CONCLUSION

Our results identified the role of the miR-30c/TWF1 axis in pancreatic cancer progression and demonstrated that miR-30c might serve as a prognostic biomarker and therapeutic target for pancreatic cancer.

背景

已有研究报道，miR-30c（微小 RNA-30c）在多种癌症的发生和发展中具有重要作用。

目的

研究 miR-30c 在胰腺癌中的临床意义和作用。

方法

通过基因表达综合数据库分析 miR-30c 和 twinfilin 1（TWF1）的表达水平，并通过实时定量聚合酶链反应（RT-qPCR）在人胰腺癌中进行验证。通过 CCK-8 和流式细胞术检测 miR-30c 对胰腺癌细胞生长、凋亡和细胞周期的影响。此外，通过皮下移植实验进行了研究。利用靶基因预测软件和荧光素酶报告实验鉴定 TWF1 是 miR-30c 的直接靶基因。

结果

miR-30c 在胰腺癌组织中表达显著下调，与生存相关。增益和失能实验表明，miR-30c 抑制胰腺癌细胞增殖和迁移。RT-qPCR、Western blot 和荧光素酶报告实验表明，miR-30c 可直接靶向 TWF1。胰腺癌组织中 miR-30c 的表达水平与 TWF1 的表达呈负相关。此外，外源性 miR-30c 的作用可被 TWF1 过表达所挽救。