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MicroRNA-520a 通过靶向 RRM2/Wnt 轴抑制非小细胞肺癌的发病和进展。

MicroRNA-520a Suppresses Pathogenesis and Progression of Non-Small-Cell Lung Cancer through Targeting the RRM2/Wnt Axis.

机构信息

Department of Respiratory Oncology, Shandong Provincial Chest Hospital, Jinan, 250013 Shandong, China.

Department of Tuberculosis, Shandong Provincial Chest Hospital, Jinan, 250013 Shandong, China.

出版信息

Anal Cell Pathol (Amst). 2021 Mar 30;2021:9652420. doi: 10.1155/2021/9652420. eCollection 2021.

Abstract

MicroRNAs (miRNAs) regulate multiple cellular behaviors, and their aberrant expression is frequently associated with disease progression. This research focused on the effects of miR-520a on the development of non-small-cell lung cancer (NSCLC) and the molecules involved. Tumor and normal tissues from 24 patients with NSCLC were collected. Differentially expressed miRNAs between tumor tissues and normal tissues were screened using microarrays, and miR-520a was screened to be significantly poorly expressed in tumor samples. Artificial upregulation of miR-520a reduced proliferation, migration and invasion, and resistance to death of NSCLC A549 and H460 cells according to the MTT, EdU labeling, transwell, and flow cytometry assays, respectively. miR-520a upregulation suppressed growth and metastasis of xenograft tumors in vivo. The integrated bioinformatic analysis and dual luciferase assays suggested that miR-520a targeted ribonucleotide reductase subunit 2 (RRM2) mRNA and inactivated the Wnt/-catenin signaling pathway in NSCLC cells. Upregulation of RRM2 enhanced the malignant behaviors of NSCLCs, but the oncogenic effects of RRM2 were blocked upon miR-520a overexpression. To conclude, this study evidenced that miR-520a inhibits NSCLC progression through suppressing RRM2 and the Wnt signaling pathway. This paper may offer novel insights into NSCLC treatment.

摘要

微小 RNA(miRNA)调节多种细胞行为,其异常表达常与疾病进展有关。本研究聚焦于 miR-520a 对非小细胞肺癌(NSCLC)发展的影响及其涉及的分子。收集了 24 例 NSCLC 患者的肿瘤和正常组织。通过微阵列筛选肿瘤组织和正常组织之间差异表达的 miRNA,筛选出 miR-520a 在肿瘤样本中表达明显下调。MTT、EdU 标记、Transwell 和流式细胞术分别证实,人工上调 miR-520a 可降低 NSCLC A549 和 H460 细胞的增殖、迁移和侵袭能力,并提高其对死亡的抵抗能力。miR-520a 的上调抑制了体内异种移植肿瘤的生长和转移。整合的生物信息学分析和双荧光素酶报告基因实验表明,miR-520a 靶向核糖核苷酸还原酶亚基 2(RRM2)mRNA,并在 NSCLC 细胞中失活 Wnt/-连环蛋白信号通路。RRM2 的上调增强了 NSCLC 的恶性行为,但 miR-520a 过表达阻断了 RRM2 的致癌作用。总之,本研究证明 miR-520a 通过抑制 RRM2 和 Wnt 信号通路抑制 NSCLC 的进展。本文可能为 NSCLC 的治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d2b/8026327/160d170fd9f6/ACP2021-9652420.001.jpg

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