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长链基因间非编码RNA-p21通过降低非小细胞肺癌中PUMA的表达来抑制细胞凋亡。

Long intergenic noncoding RNA-p21 inhibits apoptosis by decreasing PUMA expression in non-small cell lung cancer.

作者信息

Yang Tao, Zhang Wenjun, Wang Li, Xiao Chunyan, Guo Bingling, Gong Yi, Liang Xiping, Huang Dehong, Li Qiying, Nan Yingyu, Xiang Ying, Shao Jianghe

机构信息

1 Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing Cancer Institute, Chongqing Cancer Hospital, Chongqing, China.

2 Department of Oncology, Chongqing General Hospital, Chongqing, China.

出版信息

J Int Med Res. 2019 Jan;47(1):481-493. doi: 10.1177/0300060518816592. Epub 2018 Dec 16.

DOI:10.1177/0300060518816592
PMID:30556447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6384454/
Abstract

OBJECTIVE

Long noncoding RNAs (lncRNAs) are important mediators in tumor progression. Long intergenic noncoding RNA-p21 (lincRNA-p21) participates in multiple biological processes. This study explored the role of lincRNA-p21 in human non-small cell lung cancer (NSCLC) progression and potential regulatory mechanisms.

METHODS

LincRNA-p21 expression in NSCLC tissues and cell lines (A549, H1299, H1650, and NCI-H2087) was determined by quantitative real-time PCR. LincRNA-p21 overexpressing and sh-lincRNA-p21 lentiviral were respectively transfected into H1299 and A549 cells. Flow cytometry was used to measure apoptosis. Microarray analysis and RNA pull-down assay were used to predict the target genes of lincRNA-p21. Finally, PUMA siRNA and overexpressing PUMA were transfected into NSCLC cells, and the extent of cell apoptosis was measured. The protein expression levels of the relative genes were confirmed by western blot analysis.

RESULTS

LincRNA-p21 was significantly upregulated in NSCLC tissues and cells. The upregulation of lincRNA-p21 considerably inhibited cell apoptosis while the downregulation of lincRNA-p21 showed the opposite effect. PUMA was a direct target gene of lincRNA-p21 and was negatively correlated with lincRNA-p21 in NSCLC specimens. The anti-apoptotic effect of lincRNA-p21 can be effectively attenuated by the upregulation of PUMA.

CONCLUSION

LincRNA-p21 is aberrantly upregulated in NSCLC and inhibits cell apoptosis by decreasing PUMA expression.

摘要

目的

长链非编码RNA（lncRNAs）是肿瘤进展中的重要介质。长链基因间非编码RNA-p21（lincRNA-p21）参与多种生物学过程。本研究探讨lincRNA-p21在人类非小细胞肺癌（NSCLC）进展中的作用及潜在调控机制。

方法

采用定量实时PCR检测NSCLC组织及细胞系（A549、H1299、H1650和NCI-H2087）中lincRNA-p21的表达。将lincRNA-p21过表达慢病毒和sh-lincRNA-p21慢病毒分别转染至H1299和A549细胞。采用流式细胞术检测细胞凋亡。利用基因芯片分析和RNA下拉试验预测lincRNA-p21的靶基因。最后，将PUMA siRNA和过表达PUMA转染至NSCLC细胞，检测细胞凋亡程度。通过蛋白质免疫印迹分析确认相关基因的蛋白表达水平。

结果

lincRNA-p21在NSCLC组织和细胞中显著上调。lincRNA-p21的上调显著抑制细胞凋亡，而lincRNA-p21的下调则产生相反的效果。PUMA是lincRNA-p21的直接靶基因，在NSCLC标本中与lincRNA-p21呈负相关。上调PUMA可有效减弱lincRNA-p21的抗凋亡作用。

结论

lincRNA-p21在NSCLC中异常上调，并通过降低PUMA表达抑制细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/e4cec1892e19/10.1177_0300060518816592-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/d4f11d289290/10.1177_0300060518816592-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/72c64966dcf3/10.1177_0300060518816592-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/c6e03a75e5f0/10.1177_0300060518816592-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/e4cec1892e19/10.1177_0300060518816592-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/d4f11d289290/10.1177_0300060518816592-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/72c64966dcf3/10.1177_0300060518816592-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/c6e03a75e5f0/10.1177_0300060518816592-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adc6/6384454/e4cec1892e19/10.1177_0300060518816592-fig4.jpg

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