Abstract
Long non-coding RNAs (lncRNAs) are associated with the occurrence, development and prognoses of non-small cell lung cancer (NSCLC). In the present study, we investigated the functional mechanisms of the lncRNA XIST in two human NSCLC cell lines, A549 and NCI-H1299. In all the 5 NSCLC cell lines (NL9980, NCI-H1299, NCI-H460, SPC-A-1 and A549) tested, the expression levels of XIST were significantly elevated, as compared with those in normal human bronchial epithelial cell line BEAS-2B. In A549 and NCI-H1299 cells, knockdown of XIST by siRNA significantly inhibited the cell proliferation, migration and invasion, and promoted cell apoptosis. Furthermore, XIST knockdown elevated the expression of E-cadherin, and suppressed the expression of Bcl-2. Moreover, knockdown of XIST significantly suppressed the tumor growth in NSCLC A549 xenograft mouse model. Bioinformatic analysis and luciferase reporter assays revealed that XIST was negatively regulated by miR-449a. We further identified reciprocal repression between XIST and miR-449a, which eventually influenced the expression of Bcl-2: XIST functioned as a miRNA sponge of miR-449a, which was a negative regulator of Bcl-2. These data show that expression of the lncRNA XIST is associated with an increased growth rate and metastatic potential in NSCLC A549 and NCI-H1299 cells partially through miR-449a, and suggest that XIST may be a potential prognostic factor and therapeutic target for patients with NSCLC.
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01 March 2017
This article has been corrected since Advanced Online Publication, and an erratum is also printed in this issue.
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Acknowledgements
This study was supported by grants from the Ministry of Education Fund Priority to the Development of Instructions of Higher Leading Doctoral Degree Field (No 20131202130001, to Qing-hua ZHOU), the National Natural Science Foundation of China (No 81572288, to Qing-hua ZHOU; No 81302002, to Xue-bing LI), the Tianjin Natural Science Foundation (No 14JCQNJC12300, to Xue-bing LI) and the “New Century” Talent Training Project of Tianjin Medical University General Hospital (2014, to Xue-bing LI).
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Supplementary information is available on the website of Acta Pharmacologica Sinica.
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Supplementary Table 1
Sequences of siRNA for knockdown of XIST. (DOC 29 kb)
Supplementary Table 2
Sequences of shRNA embedded in lentivirus for knockdown of XIST. (DOC 29 kb)
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Zhang, Yl., Li, Xb., Hou, Yx. et al. The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer. Acta Pharmacol Sin 38, 371–381 (2017). https://doi.org/10.1038/aps.2016.133
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DOI: https://doi.org/10.1038/aps.2016.133
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