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miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1

Radioresistance represents a major obstacle in cancer treatment, the underlying mechanism of which is complex and not well understood. miR-148b has been reported to be implicated regulating radioresistance in lymphoma cells. However, this function has not been investigated in lung cancer cells. Micr...

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Autores principales: Zhai, Guangsheng, Li, Gaozhong, Xu, Bo, Jia, Tongfu, Sun, Yinping, Zheng, Jianbo, Li, Jianbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293578/
https://www.ncbi.nlm.nih.gov/pubmed/26759383
http://dx.doi.org/10.1042/BSR20150300
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author Zhai, Guangsheng
Li, Gaozhong
Xu, Bo
Jia, Tongfu
Sun, Yinping
Zheng, Jianbo
Li, Jianbin
author_facet Zhai, Guangsheng
Li, Gaozhong
Xu, Bo
Jia, Tongfu
Sun, Yinping
Zheng, Jianbo
Li, Jianbin
author_sort Zhai, Guangsheng
collection PubMed
description Radioresistance represents a major obstacle in cancer treatment, the underlying mechanism of which is complex and not well understood. miR-148b has been reported to be implicated regulating radioresistance in lymphoma cells. However, this function has not been investigated in lung cancer cells. Microarray analysis was performed in A549 cells 48 h after exposure to 8 Gy of γ-irradiation or sham irradiation to identify differentially expressed miRNAs. miR-148b mimic and inhibitor were transfected, followed by clonogenic survival assay to examine response to irradiation in A549 cells. Western Blot and luciferase assay were performed to investigate the direct target of miR-148b. Xenograft mouse models were used to examine in vivo function of miR-148b. Our data showed that expression of miR-148b was significantly down-regulated in both serum and cancerous tissues of radioresistant lung cancer patients compared with radiosensitive patients. Overexpression of miR-148b reversed radioresistance in A549 cells. MutL homologue 1 (MLH1) is the direct target of miR-148b which is required for the regulatory role of miR-148b in radioresistance. miR-148b mimic sensitized A549 xenografts to irradiation in vivo. Our study demonstrated that miR-148b regulates radioresistance of lung cancer cells by modulating MLH1 expression level. miR-148b may represent a new therapeutic target for the intervention of lung cancer.
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spelling pubmed-52935782017-02-14 miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1 Zhai, Guangsheng Li, Gaozhong Xu, Bo Jia, Tongfu Sun, Yinping Zheng, Jianbo Li, Jianbin Biosci Rep Original Papers Radioresistance represents a major obstacle in cancer treatment, the underlying mechanism of which is complex and not well understood. miR-148b has been reported to be implicated regulating radioresistance in lymphoma cells. However, this function has not been investigated in lung cancer cells. Microarray analysis was performed in A549 cells 48 h after exposure to 8 Gy of γ-irradiation or sham irradiation to identify differentially expressed miRNAs. miR-148b mimic and inhibitor were transfected, followed by clonogenic survival assay to examine response to irradiation in A549 cells. Western Blot and luciferase assay were performed to investigate the direct target of miR-148b. Xenograft mouse models were used to examine in vivo function of miR-148b. Our data showed that expression of miR-148b was significantly down-regulated in both serum and cancerous tissues of radioresistant lung cancer patients compared with radiosensitive patients. Overexpression of miR-148b reversed radioresistance in A549 cells. MutL homologue 1 (MLH1) is the direct target of miR-148b which is required for the regulatory role of miR-148b in radioresistance. miR-148b mimic sensitized A549 xenografts to irradiation in vivo. Our study demonstrated that miR-148b regulates radioresistance of lung cancer cells by modulating MLH1 expression level. miR-148b may represent a new therapeutic target for the intervention of lung cancer. Portland Press Ltd. 2016-06-30 /pmc/articles/PMC5293578/ /pubmed/26759383 http://dx.doi.org/10.1042/BSR20150300 Text en © 2016 Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article published by Portland Press Limited and distributed under the Creative Commons Attribution Licence 3.0 (http://creativecommons.org/licenses/by/3.0/) .
spellingShingle Original Papers
Zhai, Guangsheng
Li, Gaozhong
Xu, Bo
Jia, Tongfu
Sun, Yinping
Zheng, Jianbo
Li, Jianbin
miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1
title miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1
title_full miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1
title_fullStr miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1
title_full_unstemmed miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1
title_short miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1
title_sort mirna-148b regulates radioresistance in non-small lung cancer cells via regulation of mutl homologue 1
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293578/
https://www.ncbi.nlm.nih.gov/pubmed/26759383
http://dx.doi.org/10.1042/BSR20150300
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