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长链非编码RNA GATA6-AS1通过抑制微小RNA-543上调RKIP来抑制非小细胞肺癌的进展。

LncRNA GATA6-AS1 Inhibits the Progression of Non-Small Cell Lung Cancer via Repressing microRNA-543 to Up-Regulating RKIP.

作者信息

Gong Zixuan, Chen Xiaoyu, Zhang YueChao, Liu Cheng, Wang Zhibing, Xu Xiaoyan, Zhu Jun, Xue Tongqing

机构信息

Department of Urology, Jiangsu Provincial People's Hospital, Nanjing, Jiangsu Province, 211166, People's Republic of China.

Department of Radiology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huaian 223001, Jiangsu Province, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Sep 29;12:9327-9338. doi: 10.2147/CMAR.S254184. eCollection 2020.

DOI:10.2147/CMAR.S254184
PMID:33061622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7532887/
Abstract

BACKGROUND

Much evidence unveils the significance of long non-coding RNAs (lncRNAs) in diverse cancers. This study was designed to clarify the function and mechanism of lncRNA GATA6 antisense RNA 1 (GATA6-AS1) in the progression of non-small cell lung cancer (NSCLC).

METHODS

GATA6-AS1, miR-543 and Raf kinase inhibitor protein () mRNA expressions were detected by qRT-PCR. Chi-square test was adopted to analyze the relationship between GATA6-AS1 expression and the clinicopathological parameters of NSCLC patients. NSCLC cells H1299 and H460 cells were used as overexpression or knockdown models, respectively, and cell proliferation and metastasis were determined by CCK-8 and Transwell assays. , , , , expressions in NSCLC cells were detected by Western blot. The targeting relationship between GATA6-AS1 and miR-543 was confirmed by dual-luciferase reporter assay.

RESULTS

GATA6-AS1 was significantly lowly expressed in NSCLC tissues and cell lines, and its low expression level was significantly correlated with larger tumor size and positive lymph node metastasis. GATA6-AS1 overexpression inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition of NSCLC cells, while GATA6-AS1 knockdown caused the opposite effects. Mechanistically, it was confirmed that GATA6-AS1 impeded NSCLC cell proliferation and metastasis by adsorbing miR-543 and up-regulating the expression of .

CONCLUSIONS

As a tumor suppressor, GATA6-AS1 participates in suppressing the progression of NSCLC by modulating the miR-543/ axis.

摘要

背景

大量证据揭示了长链非编码RNA（lncRNAs）在多种癌症中的重要性。本研究旨在阐明lncRNA GATA6反义RNA 1（GATA6-AS1）在非小细胞肺癌（NSCLC）进展中的功能及机制。

方法

采用qRT-PCR检测GATA6-AS1、miR-543和Raf激酶抑制蛋白（RKIP）mRNA表达。采用卡方检验分析GATA6-AS1表达与NSCLC患者临床病理参数之间的关系。分别将NSCLC细胞H1299和H460细胞用作过表达或敲低模型，通过CCK-8和Transwell实验检测细胞增殖和转移情况。通过蛋白质免疫印迹法检测NSCLC细胞中RKIP、p-AKT、AKT、p-ERK、ERK的表达。通过双荧光素酶报告基因实验证实GATA6-AS1与miR-543之间的靶向关系。

结果

GATA6-AS1在NSCLC组织和细胞系中显著低表达，其低表达水平与更大的肿瘤大小和阳性淋巴结转移显著相关。GATA6-AS1过表达抑制NSCLC细胞的增殖、迁移、侵袭和上皮-间质转化，而GATA6-AS1敲低则产生相反的效果。机制上，证实GATA6-AS1通过吸附miR-543并上调RKIP的表达来阻碍NSCLC细胞的增殖和转移。

结论

作为一种肿瘤抑制因子，GATA6-AS1通过调节miR-543/RKIP轴参与抑制NSCLC的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/49cc66c73c0a/CMAR-12-9327-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/5580c5e7819e/CMAR-12-9327-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/b2ad3357ba12/CMAR-12-9327-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/63005ebacf47/CMAR-12-9327-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/a4ed0376ecab/CMAR-12-9327-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/515ccadd2c48/CMAR-12-9327-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/49cc66c73c0a/CMAR-12-9327-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/5580c5e7819e/CMAR-12-9327-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/b2ad3357ba12/CMAR-12-9327-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/63005ebacf47/CMAR-12-9327-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/a4ed0376ecab/CMAR-12-9327-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/515ccadd2c48/CMAR-12-9327-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1158/7532887/49cc66c73c0a/CMAR-12-9327-g0006.jpg

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