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MicroRNA-154 作为膀胱癌的一个预后因素,通过靶向 RSF1 和 RUNX2 抑制细胞恶性程度。

MicroRNA-154 as a prognostic factor in bladder cancer inhibits cellular malignancy by targeting RSF1 and RUNX2.

机构信息

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

出版信息

Oncol Rep. 2017 Nov;38(5):2727-2734. doi: 10.3892/or.2017.5992. Epub 2017 Sep 25.

Abstract

Recent studies have demonstrated that microRNA-154 (miR-154) is involved in tumorigenesis, progression, invasion and metastasis in several types of human cancer. However, whether it plays a role in bladder cancer (BC) is unclear. The aim of the present study was to determine miR-154 levels in human BC tissues and investigate the correlation between miR-154 levels and clinicopathological characteristics as well as patient outcome. Using RT-qPCR, we found that the expression levels of miR-154 were significantly lower in BC tissues compared to adjacent normal tissues. We also demonstrated that downregulation of miR-154 was associated with advanced clinicopathological features and worse prognoses for patients with BC. Using a variety of integrated approaches, we demonstrated that both runt-related transcription factor 2 (RUNX2) and remodeling and spacing factor 1 (RSF1) were miR-154 targets. Notably, there was an inverse correlation between RSF1, RUNX2 and miR-154 expression in BC tissues. The biological functions of miR-154 were examined in vitro using Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays with T24 human bladder carcinoma cells transfected with miR-154 mimics or negative controls. These assays demonstrated that miR-154 significantly suppressed proliferation, migration and invasion of T24 cells (P<0.05). Furthermore, overexpression of RSF1 and RUNX2 rescued miR-154-induced inhibition of these aggressive behaviors. Our results indicated that miR-154, and its downstream targets RSF1 and RUNX2, are promising options for future BC therapies.

摘要

最近的研究表明,microRNA-154(miR-154)参与了多种人类癌症的肿瘤发生、进展、侵袭和转移。然而,它是否在膀胱癌(BC)中发挥作用尚不清楚。本研究旨在确定人膀胱癌组织中 miR-154 的水平,并探讨 miR-154 水平与临床病理特征以及患者预后的相关性。通过 RT-qPCR,我们发现 miR-154 的表达水平在膀胱癌组织中明显低于相邻正常组织。我们还表明,miR-154 的下调与晚期临床病理特征和膀胱癌患者的预后不良有关。通过多种综合方法,我们证明 runt 相关转录因子 2(RUNX2)和重塑和间隔因子 1(RSF1)均为 miR-154 的靶标。值得注意的是,在膀胱癌组织中,RSF1、RUNX2 和 miR-154 的表达呈负相关。通过使用 Cell Counting Kit-8(CCK-8)、划痕愈合和 Transwell 测定法,用 miR-154 模拟物或阴性对照转染 T24 人膀胱癌细胞,在体外研究了 miR-154 的生物学功能。这些测定表明,miR-154 显著抑制 T24 细胞的增殖、迁移和侵袭(P<0.05)。此外,RSF1 和 RUNX2 的过表达挽救了 miR-154 诱导的这些侵袭性行为的抑制。我们的结果表明,miR-154 及其下游靶标 RSF1 和 RUNX2 是未来 BC 治疗的有前途的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e86b/5780025/54f5f6d3803c/OR-38-05-2727-g00.jpg

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