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miR-211-5p 在膀胱癌中下调并作为一种预后标志物。

miR-211-5p is down-regulated and a prognostic marker in bladder cancer.

机构信息

Department of Urinary Surgery, The Qujing No. 1 People's Hospital, Qujing, Yunnan Province, China.

出版信息

J Gene Med. 2020 Dec;22(12):e3270. doi: 10.1002/jgm.3270. Epub 2020 Sep 28.

Abstract

BACKGROUND

The micro RNA (miRNA)/histone deacetylase 9 (HDAC9) signaling axis has been reported to be involved in initiating and developing multiple malignant tumors. In the present study, we aimed to determine whether miR-211-5p serves as a post-transcriptional regulator in bladder cancer (BCa) cell proliferation and apoptosis by targeting HDAC9.

METHODS

miRNA expression profiling of BCa tissues and para-carcinoma tissues was screened by miRNA microarray. After transfection with miR-211-5p mimics or short hairpin RNA of HDAC9 (sh-HDAC9), mRNA and protein expression was evaluated using a quantitative reverse transcription-polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm was used, and a dual-luciferase reporter assay was performed to validate HDAC9 as a direct target of miR-211-5p. Cell proliferation was analyzed by the 3-(4, 5-dimethylthiazl2-yl)-2,5-diphenyltetazolium bromide (MTT) assay. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) detection was used to evaluate apoptosis in 5637 and T24 cells. A transwell assay was used to assess migration and invasion.

RESULTS

miR-211-5p is down-regulated in BCa tumor tissues and cell lines. miR-211-5p is identified as an independent biomarker for predicting overall survival. HDAC9 is a direct target of miR-211-5p, and overexpression of miR-211-5p represses HDAC9 protein expression in vitro. Overexpression of miR-211-5p or HDAC9 knockdown significantly inhibits proliferation, migration and invasion of 5637 and T24 cells, and also induces cell apoptosis.

CONCLUSIONS

miR-211-5p may play a role as a tumor suppressor and as a favourable prognostic marker in BCa.

摘要

背景

微小 RNA(miRNA)/组蛋白去乙酰化酶 9(HDAC9)信号轴已被报道参与多种恶性肿瘤的发生和发展。在本研究中,我们旨在通过靶向 HDAC9 来确定 miR-211-5p 是否作为膀胱癌(BCa)细胞增殖和凋亡的转录后调节因子。

方法

通过 miRNA 微阵列筛选 BCa 组织和癌旁组织的 miRNA 表达谱。转染 miR-211-5p 模拟物或 HDAC9 的短发夹 RNA(sh-HDAC9)后,分别通过定量逆转录聚合酶链反应和 Western 印迹评估 mRNA 和蛋白表达。使用生物信息学算法,并通过双荧光素酶报告基因检测验证 HDAC9 是 miR-211-5p 的直接靶标。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定分析细胞增殖。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记(TUNEL)检测用于评估 5637 和 T24 细胞中的凋亡。Transwell 测定用于评估迁移和侵袭。

结果

miR-211-5p 在 BCa 肿瘤组织和细胞系中下调。miR-211-5p 被鉴定为预测总生存期的独立生物标志物。HDAC9 是 miR-211-5p 的直接靶标,体外过表达 miR-211-5p 抑制 HDAC9 蛋白表达。过表达 miR-211-5p 或敲低 HDAC9 可显著抑制 5637 和 T24 细胞的增殖、迁移和侵袭,并诱导细胞凋亡。

结论

miR-211-5p 可能在 BCa 中作为肿瘤抑制因子和有利的预后标志物发挥作用。

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