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微小 RNA-190b 的表达通过靶向 MEF2C 和 TCF4 预测胰腺癌的良好预后并减弱其恶性进展。

MicroRNA‑190b expression predicts a good prognosis and attenuates the malignant progression of pancreatic cancer by targeting MEF2C and TCF4.

机构信息

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

Department of Stem Cell and Regeneration, College of Basic Medical Science of China Medical University, Shenyang, Liaoning 110122, P.R. China.

出版信息

Oncol Rep. 2022 Jan;47(1). doi: 10.3892/or.2021.8223. Epub 2021 Nov 15.

Abstract

MicroRNAs (miRNAs/miRs) are key components of regulatory networks in cancer. Although miR‑190b is an important tumor‑related miRNA, its role in pancreatic cancer has not been extensively investigated. The aim of the present study was to examine the expression of miR‑190b in pancreatic cancer cell lines and tissues and evaluate its effects on cancer progression. Reverse transcription‑quantitative PCR (RT‑qPCR) analysis was used to measure miR‑190b expression levels in human pancreatic cancer cell lines and tissues, and the association between miR‑190b expression and clinicopathological characteristics was assessed. An Transwell invasion assay and an metastasis formation assay were performed using pancreatic cancer cells. The effect of miR‑190b on pancreatic cancer cell proliferation was evaluated using a Cell Counting Kit‑8 assay based on an xenograft mouse model. The direct targets of miR‑190b were predicted using bioinformatics tools and were validated through western blotting and luciferase reporter assays. Pancreatic cancer cell lines and tissues were found to express lower levels of miR‑190b compared with normal cells and adjacent non‑tumor tissues. Furthermore, high expression of miR‑190b was found to be positively correlated with low T, N and American Joint Committee on Cancer classifications, and predicted a good prognosis. miR‑190b was shown to exert suppressive effects on cancer cell proliferation, invasion and metastasis. In addition, it was also found that miR‑190b directly targeted myocyte enhancer factor 2C (MEF2C) and transcription factor 4 (TCF4) in pancreatic cancer, thus serving as a tumor suppressor and a predictor of good prognosis in pancreatic cancer. The immunohistochemistry and RT‑qPCR results indicated that the MEF2C and TCF4 expression levels were negatively correlated with the miR‑190b expression levels. The findings of the present study highlight the value of miR‑190b as a novel target candidate for pancreatic cancer diagnosis and therapy.

摘要

微小 RNA(miRNA/miRs)是癌症调控网络的关键组成部分。尽管 miR-190b 是一种重要的肿瘤相关 miRNA,但它在胰腺癌中的作用尚未得到广泛研究。本研究旨在检测 miR-190b 在胰腺癌细胞系和组织中的表达,并评估其对癌症进展的影响。采用逆转录-定量 PCR(RT-qPCR)分析检测人胰腺癌细胞系和组织中 miR-190b 的表达水平,并评估 miR-190b 表达与临床病理特征的相关性。采用 Transwell 侵袭实验和转移形成实验检测胰腺癌细胞。基于异种移植小鼠模型,通过细胞计数试剂盒-8 实验评估 miR-190b 对胰腺癌细胞增殖的影响。使用生物信息学工具预测 miR-190b 的直接靶标,并通过 Western blot 和荧光素酶报告基因实验进行验证。与正常细胞和相邻非肿瘤组织相比,胰腺癌细胞系和组织中 miR-190b 的表达水平较低。此外,高表达 miR-190b 与低 T、N 和美国癌症联合委员会分类呈正相关,预示着良好的预后。miR-190b 对癌细胞增殖、侵袭和转移具有抑制作用。此外,还发现 miR-190b 直接靶向肌细胞增强因子 2C(MEF2C)和转录因子 4(TCF4)在胰腺癌中,因此作为肿瘤抑制因子和胰腺癌良好预后的预测因子。免疫组织化学和 RT-qPCR 结果表明,MEF2C 和 TCF4 的表达水平与 miR-190b 的表达水平呈负相关。本研究结果强调了 miR-190b 作为胰腺癌诊断和治疗新靶标的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/241c/8600408/6431d28b7419/or-47-01-08223-g00.jpg

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