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长链非编码 RNA RP11-805J14.5 通过海绵吸附 miR-34b-3p 和 miR-139-5p 来调节肺腺癌中的 CCND2 发挥 ceRNA 作用。

LncRNA RP11‑805J14.5 functions as a ceRNA to regulate CCND2 by sponging miR‑34b‑3p and miR‑139‑5p in lung adenocarcinoma.

机构信息

Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China.

Department of Thoracic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang 315010, P.R. China.

出版信息

Oncol Rep. 2022 Sep;48(3). doi: 10.3892/or.2022.8376. Epub 2022 Jul 22.

DOI:10.3892/or.2022.8376
PMID:35866595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9350987/
Abstract

Lung adenocarcinoma (LUAD) is the most common lung cancer with high incidence. The prognosis of LUAD is poor due to its aggressive behavior. Long non‑coding RNAs (lncRNAs) have been reported as a key modulator on LUAD progression. Therefore, the present study aimed to clarify the molecular mechanism of lncRNAs in LUAD development. The expression of lncRNA RP11‑805J14.5 (RP11‑805J14.5) in LUAD tissues and cells was quantified based on the data in The Cancer Genome Atlas (TCGA). Cell viability was determined using Cell Counting Kit‑8 method. Apoptotic cells were sorted and determined by flow cytometry. Cell migration and invasion abilities were detected by the Transwell assay. Luciferase reporter experiment and RNA pull‑down assay were utilized to determine the interactions between RP11‑805J14.5, microRNA (miR)‑34b‑3p, miR‑139‑5p, and cyclin D2 (CCND2). A xenograft tumor was established to determine tumor growth . RP11‑805J14.5 was highly expressed in LUAD and associated with poor survival of LUAD patients. Knockdown of RP11‑805J14.5 suppressed LUAD cell growth, invasion, migration and tumor growth, indicating that RP11‑805J14.5 is an important regulator of LUAD. Our study demonstrated that the regulation of RP11‑805J14.5 on LUAD was mediated by CCND2 whose expression was regulated by sponging miR‑34b‑3p and miR‑139‑5p. The expression of RP11‑805J14.5 was increased in LUAD, and the knockdown of RP11‑805J14.5 expression suppressed LUAD cell growth, invasion and migration by downregulating CCND2 by sponging miR‑34b‑3p and miR‑139‑5p, indicating that RP11‑805J14.5 could be a prospective target for LUAD therapy.

摘要

肺腺癌(LUAD)是最常见的肺癌,发病率较高。由于其侵袭性行为,LUAD 的预后较差。长链非编码 RNA(lncRNA)已被报道为 LUAD 进展的关键调节因子。因此,本研究旨在阐明 lncRNA 在 LUAD 发展中的分子机制。根据癌症基因组图谱(TCGA)中的数据,定量检测 LUAD 组织和细胞中 lncRNA RP11-805J14.5(RP11-805J14.5)的表达。通过细胞计数试剂盒-8 法测定细胞活力。通过流式细胞术分选和测定凋亡细胞。通过 Transwell 测定法检测细胞迁移和侵袭能力。利用荧光素酶报告实验和 RNA 下拉实验来确定 RP11-805J14.5、微小 RNA(miR)-34b-3p、miR-139-5p 和细胞周期蛋白 D2(CCND2)之间的相互作用。建立异种移植肿瘤以确定肿瘤生长情况。RP11-805J14.5 在 LUAD 中高表达,并与 LUAD 患者的不良生存相关。敲低 RP11-805J14.5 抑制 LUAD 细胞生长、侵袭、迁移和肿瘤生长,表明 RP11-805J14.5 是 LUAD 的重要调节剂。我们的研究表明,RP11-805J14.5 对 LUAD 的调节是通过 CCND2 介导的,其表达受海绵 miR-34b-3p 和 miR-139-5p 的调节。在 LUAD 中,RP11-805J14.5 的表达增加,敲低 RP11-805J14.5 表达通过海绵 miR-34b-3p 和 miR-139-5p 下调 CCND2 抑制 LUAD 细胞生长、侵袭和迁移,表明 RP11-805J14.5 可能成为 LUAD 治疗的有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/fe612327843c/or-48-03-08376-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/25aac70e39a9/or-48-03-08376-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/49aefc63a1ad/or-48-03-08376-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/20285302ab8a/or-48-03-08376-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/7d172b47ed2e/or-48-03-08376-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/fe612327843c/or-48-03-08376-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/25aac70e39a9/or-48-03-08376-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/49aefc63a1ad/or-48-03-08376-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/20285302ab8a/or-48-03-08376-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/7d172b47ed2e/or-48-03-08376-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbeb/9350987/fe612327843c/or-48-03-08376-g04.jpg

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