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微小 RNA-34a-5p 通过沉默基质金属蛋白酶-2 来调节膀胱癌细胞的运动性,从而发挥肿瘤抑制作用。

MicroRNA‑34a‑5p serves as a tumor suppressor by regulating the cell motility of bladder cancer cells through matrix metalloproteinase‑2 silencing.

机构信息

Division of Urology, Department of Surgery, Shin Kong Wu Ho‑Su Memorial Hospital, Taipei 11102, Taiwan, R.O.C.

Translational Medicine Center, Shin Kong Wu Ho‑Su Memorial Hospital, Taipei 11102, Taiwan, R.O.C.

出版信息

Oncol Rep. 2021 Mar;45(3):911-920. doi: 10.3892/or.2020.7910. Epub 2020 Dec 24.

Abstract

Bladder cancer (BC), a common urologic cancer, is the fifth most frequently diagnosed tumor worldwide. hsa‑miR‑34a displays antitumor activity in several types of cancer. However, the functional mechanisms underlying hsa‑miR‑34a in BC remains largely unknown. We observed that hsa‑mir‑34a levels were significantly and negatively associated with clinical disease stage as well as regional lymph node metastasis in human BC. In a series of in vitro investigations, overexpression of hsa‑miR‑34a inhibited cell migration and invasion in BC cell lines 5637 and UMUC3 as detected by Transwell assays. We further found that hsa‑miR‑34a inhibited cell migration and invasion by silencing matrix metalloproteinase‑2 (MMP‑2) expression and thus interrupting MMP‑2‑mediated cell motility. Our analysis of BC datasets from The Cancer Genome Atlas database revealed a negative correlation between hsa‑miR‑34a and MMP‑2. Moreover, higher MMP‑2 protein expression was observed in the BC tissues when compared with that noted in the normal tissue. MMP‑2 levels were also significantly associated with clinical disease stage and poor survival rate in human BC. These findings indicate that MMP‑2 plays a critical role in regulating BC progression. Therefore, hsa‑miR‑34a is a promising treatment to target MMP‑2 for the prevention and inhibition of cell migration and invasion in BC.

摘要

膀胱癌(BC)是一种常见的泌尿系统癌症,是全球第五大最常见的肿瘤。hsa-miR-34a 在几种类型的癌症中具有抗肿瘤活性。然而,hsa-miR-34a 在 BC 中的功能机制在很大程度上尚不清楚。我们观察到 hsa-miR-34a 的水平与人类 BC 的临床疾病分期以及局部淋巴结转移呈显著负相关。在一系列体外研究中,通过 Transwell 分析发现,hsa-miR-34a 的过表达抑制了 BC 细胞系 5637 和 UMUC3 中的细胞迁移和侵袭。我们进一步发现,hsa-miR-34a 通过沉默基质金属蛋白酶-2(MMP-2)的表达并中断 MMP-2 介导的细胞迁移来抑制细胞迁移和侵袭。我们对癌症基因组图谱数据库中的 BC 数据集进行分析,结果显示 hsa-miR-34a 与 MMP-2 呈负相关。此外,与正常组织相比,BC 组织中 MMP-2 蛋白表达更高。MMP-2 水平也与人类 BC 的临床疾病分期和不良生存率显著相关。这些发现表明 MMP-2 在调节 BC 进展中起着关键作用。因此,hsa-miR-34a 是一种有前途的治疗方法,可靶向 MMP-2,以预防和抑制 BC 中的细胞迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2246/7859909/02fd44f361dc/OR-45-03-0911-g00.jpg

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