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microRNA-23B 通过下调 RUNX2 和抑制 Wnt/Β-连环蛋白信号通路抑制非小细胞肺癌的增殖、侵袭和迁移。

microRNA-23B inhibits non-small cell lung cancer proliferation, invasion and migration via downregulation of RUNX2 and inhibition of Wnt/Β-catenin signaling pathway.

机构信息

Department of Respiratory Medicine, Yantaishan Hospital, Yantai, China.

Department of Clinical Laboratory, Jinan Zhangqiu District Hospital of TCM, Jinan, China.

出版信息

J Biol Regul Homeost Agents. 2020 May-Jun;34(3):825-835. doi: 10.23812/20-11-A-34.

DOI:10.23812/20-11-A-34
PMID:32495614
Abstract

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. MicroRNAs (miRNAs/miRs) have been reported to play significant roles in the progression of human tumors, however, the expression and biological role of miR-23b in NSCLC remains elusive. Underexpression of miR-23b was detected in NSCLC tissues in comparison with the matched para-carcinoma tissues. The clinical value of miR-23b was analyzed, and the findings showed that miR-23b expression was negatively correlated with poor overall survival and malignant clinicopathologic characteristics of NSCLC patients. Furthermore, functional assays demonstrated that overexpression of miR-23b inhibited NSCLC cell viability, invasion and migration. Luciferase reporter assay and qRT-PCR revealed that RUNX2 was a functional target of miR-23b. The elevated expression of RUNX2 was positively correlated with overall survival of NSCLC patients. Additionally, Western blot analysis indicated that EMT and Wnt/β-catenin pathways were blocked by the upregulation of miR-23b. Taken together, these data demonstrated that dysregulation of miR-23b/RUNX2 signal may be a novel therapeutic target for the treatment of NSCLC.

摘要

非小细胞肺癌(NSCLC)约占所有肺癌病例的 85%。已有研究报道,microRNAs(miRNAs/miRs)在人类肿瘤的进展中发挥着重要作用,然而,miR-23b 在 NSCLC 中的表达和生物学作用仍不清楚。与配对的癌旁组织相比,NSCLC 组织中检测到 miR-23b 的表达下调。分析了 miR-23b 的临床价值,结果表明 miR-23b 的表达与 NSCLC 患者总体生存率差和恶性临床病理特征呈负相关。此外,功能分析表明,miR-23b 的过表达抑制了 NSCLC 细胞的活力、侵袭和迁移。荧光素酶报告基因检测和 qRT-PCR 显示,RUNX2 是 miR-23b 的功能靶标。RUNX2 的高表达与 NSCLC 患者的总体生存率呈正相关。此外,Western blot 分析表明,miR-23b 的上调阻断了 EMT 和 Wnt/β-catenin 通路。综上所述,这些数据表明,miR-23b/RUNX2 信号的失调可能是治疗 NSCLC 的一种新的治疗靶点。

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