Silencing of long noncoding RNA MYLK‐AS1 suppresses nephroblastoma via down‐regulation of CCNE1 through transcription factor TCF7L2,Journal of Cellular Physiology

当前位置： X-MOL 学术 › J. Cell. Physiol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Silencing of long noncoding RNA MYLK‐AS1 suppresses nephroblastoma via down‐regulation of CCNE1 through transcription factor TCF7L2
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-01-12 , DOI: 10.1002/jcp.30259
Shibo Zhu ₁ , Jingqi Zhang ₁ , Xiaofeng Gao ₁ , Xiangliang Tang ₁ , Yanhong Cui ₁ , Dian Li ₁ , Wei Jia ₁

Affiliation

Nephroblastoma, a pediatric kidney cancer, caused by pluripotent embryonic renal precursors. Long noncoding RNAs (lncRNAs) are commonly abnormal expressed in many cancers. In the present study, we fousced on one newly discrovered lncRNA, MYLK Antisense RNA 1 (MYLK‐AS1), and its functional role in proliferation and cycle distribution of nephroblastoma cells. Micorarray‐based analysis revealed the highly expressed Cyclin E1 (CCNE1) and MYLK‐AS1 in nephroblastoma. After nephroblastoma tissue sample collection, RT‐qPCR confirmed the upregulated expression of MYLK‐AS1 and CCNE1 in nephroblastoma tissues and cells. Kaplan–Meier curve exhibited that patients with elevated CCNE1 had lower overall survival rate in follow‐up study. RNA binding protein immunoprecipitation, chromatin immunoprecipitation, and dual‐luciferase reporter gene assay were employed to determine the relationship among MYLK‐AS1, TCF7L2, and CCNE1, which validated that transcription factor 7‐like 2 (TCF7L2) could specifically bind to MYLK‐AS1 and TCF7L2 could positively promote CCNE1. After gain‐ and loss‐of function assays, the conclusion that silencing of MYLK‐AS1 could inhibit expression of CCNE1 through the transcription factor TCF7L2 to regulate the cell proliferation and cell cycle distribution of nephroblastoma cells was obtained. Subsequently, the subcutaneous tumor formation ability of nephroblastoma cell in nude mice was observed and the silencing of MYLK‐AS1 exerts suppressive role in the tumorigenic ability of nephroblastoma cells in vivo. Taken together, MYLK‐AS1 constitutes a promising biomarker for the early detection and treatment of nephroblastoma.

中文翻译：

长链非编码 RNA MYLK-AS1 的沉默通过转录因子 TCF7L2 下调 CCNE1 抑制肾母细胞瘤

肾母细胞瘤，一种小儿肾癌，由多能胚胎肾前体细胞引起。长非编码 RNA (lncRNA) 在许多癌症中通常表达异常。在本研究中，我们重点研究了一种新发现的lncRNA，MYLK反义RNA 1 (MYLK-AS1)，及其在肾母细胞瘤细胞增殖和周期分布中的功能作用。基于微阵列的分析揭示了肾母细胞瘤中高表达的 Cyclin E1 (CCNE1) 和 MYLK-AS1。收集肾母细胞瘤组织样本后，RT-qPCR 证实肾母细胞瘤组织和细胞中 MYLK-AS1 和 CCNE1 表达上调。 Kaplan-Meier曲线显示CCNE1升高的患者在随访研究中总体生存率较低。采用RNA结合蛋白免疫沉淀、染色质免疫沉淀和双荧光素酶报告基因检测确定MYLK-AS1、TCF7L2和CCNE1之间的关系，验证转录因子7-like 2 (TCF7L2)可以特异性结合MYLK-AS1 TCF7L2可以正向促进CCNE1。经过功能获得和丧失实验，得出沉默MYLK-AS1可以通过转录因子TCF7L2抑制CCNE1的表达，从而调节肾母细胞瘤细胞的细胞增殖和细胞周期分布的结论。随后，在裸鼠体内观察肾母细胞瘤细胞的皮下成瘤能力，发现MYLK-AS1的沉默对肾母细胞瘤细胞体内的致瘤能力具有抑制作用。综上所述，MYLK-AS1 构成了肾母细胞瘤早期检测和治疗的有前景的生物标志物。

更新日期：2021-01-12

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11