LINC01207 通过海绵吸附 miR-525-5p 调控 ARHGAP11A 促进非小细胞肺癌的进展。

LINC01207 promotes the progression of non-small cell lung cancer via regulating ARHGAP11A by sponging miR-525-5p.

机构信息

Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Department of Respiration, Hospital of Traditional Chinese Medicine of Zhenhai, Ningbo, Zhejiang, China.

出版信息

Cancer Biomark. 2022;33(3):401-414. doi: 10.3233/CBM-203197.

DOI:10.3233/CBM-203197

PMID:34487020

Abstract

BACKGROUND

The disorder of LINC01207 has a significant regulatory effect on cancers, nevertheless its role in non-small cell lung cancer (NSCLC) have not been illustrated. This study investigated the regulatory effect of LINC01207 on NSCLC and clarify its molecular mechanism.

METHODS

Bioinformatics analysis was used to find the target lncRNA, miRNA and mRNA. LncBase and TargetScan databases predicted the relationship between LINC01207, miR-525-5p and ARHGAP11A. Dual-luciferase reporter gene assay and RNA binding protein immunoprecipitation assay were used to verify the binding relationship between genes. Fluorescence in situ hybridization assay was used to localize the expression of LINC01207 in NSCLC tissue. qRT-PCR and Western blot assays were used to measure the expression of LINC01207, miR-525-5p and ARHGAP11A. CCK-8 assay, Transwell assay and flow cytometry assay were used to detect NSCLC cell abilities. Mouse xenograft models further determined the effect of LINC01207 on the growth of NSCLC in vivo.

RESULTS

LINC01207 was up-regulated in NSCLC tissue and cells, which was mainly localized in the cytoplasm. LINC01207 knockdown could inhibit the proliferation, migration and invasion of cancer cells and induce cell apoptosis. In addition, silencing LINC01207 could suppress tumor growth in vivo. LINC01207 could sponge and inhibit the expression of miR-525-5p in NSCLC cells, and inhibiting LINC01207 and miR-525-5p simultaneously could reverse the effect of miR-525-5p on the progression of NSCLC cells. Further study on downstream target genes showed that miR-525-5p could restrain the expression of ARHGAP11A, and then affect the progression of NSCLC. LINC01207 acting as a competing endogenous RNA (ceRNA) could regulate the expression of ARHGAP11A by competitively binding with miR-525-5p.

CONCLUSION

LINC01207 regulates the progression of NSCLC by regulating the miR-525-5p/ARHGAP11A axis as a ceRNA and plays a carcinogenic role. In conclusion, our study elucidates the mechanism of LINC01207 regulating the progression of NSCLC, and provides a new idea for the diagnosis and treatment of NSCLC guided by lncRNA.

摘要

背景

LINC01207 的紊乱对癌症有显著的调节作用，然而其在非小细胞肺癌（NSCLC）中的作用尚未阐明。本研究旨在探讨 LINC01207 对 NSCLC 的调节作用，并阐明其分子机制。

方法

生物信息学分析用于寻找靶 lncRNA、miRNA 和 mRNA。LncBase 和 TargetScan 数据库预测了 LINC01207、miR-525-5p 和 ARHGAP11A 之间的关系。双荧光素酶报告基因检测和 RNA 结合蛋白免疫沉淀实验用于验证基因间的结合关系。荧光原位杂交实验用于定位 NSCLC 组织中 LINC01207 的表达。qRT-PCR 和 Western blot 实验用于检测 LINC01207、miR-525-5p 和 ARHGAP11A 的表达。CCK-8 实验、Transwell 实验和流式细胞术实验用于检测 NSCLC 细胞的能力。进一步构建小鼠异种移植模型，以确定 LINC01207 对 NSCLC 体内生长的影响。

结果

LINC01207 在 NSCLC 组织和细胞中呈上调表达，主要定位于细胞质。LINC01207 敲低可抑制癌细胞的增殖、迁移和侵袭，并诱导细胞凋亡。此外，沉默 LINC01207 可抑制体内肿瘤生长。LINC01207 可作为 ceRNA 吸附并抑制 NSCLC 细胞中 miR-525-5p 的表达，同时抑制 LINC01207 和 miR-525-5p 可逆转 miR-525-5p 对 NSCLC 细胞进展的影响。进一步研究下游靶基因表明，miR-525-5p 可抑制 ARHGAP11A 的表达，进而影响 NSCLC 的进展。LINC01207 作为竞争性内源 RNA（ceRNA），通过与 miR-525-5p 竞争结合来调节 ARHGAP11A 的表达。