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LIMD1-AS1通过hnRNP U稳定LIMD1 mRNA来抑制非小细胞肺癌进展。

LIMD1-AS1 suppressed non-small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U.

作者信息

Pan Jianyuan, Tang Yongqin, Liu Shumei, Li Lily, Yu Bo, Lu Yuanyuan, Wang Yu

机构信息

Cardiovascular Department, The Second People's Hospital of Hefei, Hefei, China.

General Surgery, The First People's Hospital of Chuzhou, Chuzhou, China.

出版信息

Cancer Med. 2020 Jun;9(11):3829-3839. doi: 10.1002/cam4.2898. Epub 2020 Apr 2.

DOI:10.1002/cam4.2898
PMID:32239804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7286462/
Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) occupies the majority of lung cancer cases and is notorious for the awful prognosis. LIM domains-containing 1 (LIMD1) is suggested as a tumor suppressor in lung cancer, but its mechanism in NSCLC remains elusive. Present study aimed to uncover the mechanism of LIMD1 in NSCLC.

METHODS

qRT-PCR was performed to analyze the level of LIMD1. The functions of LIMD1 in NSCLC cells were evaluated by CCK-8, EdU, and caspase-3 activity assays. RIP and pull-down assays were applied to determine the interaction of LIMD1 with heterogeneous nuclear ribonucleoprotein U (hnRNP U) and LIMD1-AS1.

RESULTS

LIMD1 was downregulated in NSCLC samples and cells. Functionally, LIMD1 hindered proliferation and drove apoptosis in NSCLC cells. Moreover, long noncoding RNA (lncRNA) LIMD1 antisense RNA 1 (LIMD1-AS1) was downregulated in NSCLC samples and cell lines. LIMD1-AS1 knockdown abrogated NSCLC cell growth in vitro and in vivo. Mechanistically, LIMD1-AS1 stabilized LIMD1 mRNA through interacting with hnRNP U. Rescue experiments suggested that LIMD1-AS1 repressed NSCLC progression through LIMD1.

CONCLUSIONS

LIMD1-AS1 suppressed NSCLC progression through stabilizing LIMD1 mRNA via hnRNP U, providing new thoughts for the improvement of molecular-targeted therapy for NSCLC.

摘要

背景

非小细胞肺癌（NSCLC）占肺癌病例的大多数，其预后极差，声名狼藉。含LIM结构域1（LIMD1）被认为是肺癌中的一种肿瘤抑制因子，但其在NSCLC中的作用机制仍不清楚。本研究旨在揭示LIMD1在NSCLC中的作用机制。

方法

采用qRT-PCR分析LIMD1的水平。通过CCK-8、EdU和caspase-3活性测定评估LIMD1在NSCLC细胞中的功能。应用RIP和下拉试验确定LIMD1与异质性核糖核蛋白U（hnRNP U）和LIMD1-AS1的相互作用。

结果

LIMD1在NSCLC样本和细胞中表达下调。在功能上，LIMD1抑制NSCLC细胞的增殖并诱导其凋亡。此外，长链非编码RNA（lncRNA）LIMD1反义RNA 1（LIMD1-AS1）在NSCLC样本和细胞系中表达下调。敲低LIMD1-AS1可在体外和体内消除NSCLC细胞的生长。机制上，LIMD1-AS1通过与hnRNP U相互作用稳定LIMD1 mRNA。挽救实验表明，LIMD1-AS1通过LIMD1抑制NSCLC进展。

结论

LIMD1-AS1通过hnRNP U稳定LIMD1 mRNA抑制NSCLC进展，为改善NSCLC的分子靶向治疗提供了新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/90f685e1e25b/CAM4-9-3829-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/ea2d0a7fc41a/CAM4-9-3829-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/41ae19475d25/CAM4-9-3829-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/9c8bb389d875/CAM4-9-3829-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/90f685e1e25b/CAM4-9-3829-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/ea2d0a7fc41a/CAM4-9-3829-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/41ae19475d25/CAM4-9-3829-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/9c8bb389d875/CAM4-9-3829-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784f/7286462/90f685e1e25b/CAM4-9-3829-g004.jpg

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