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MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway
BACKGROUND: MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408859/ https://www.ncbi.nlm.nih.gov/pubmed/30849960 http://dx.doi.org/10.1186/s12885-019-5400-3 |
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author | Lu, Lin Liu, Qiyao Wang, Peipei Wu, Yong Liu, Xia Weng, Chengyin Fang, Xisheng Li, Baoxiu Cao, Xiaofei Mao, Haibo Wang, Lina Guan, Mingmei Wang, Wei Liu, Guolong |
author_facet | Lu, Lin Liu, Qiyao Wang, Peipei Wu, Yong Liu, Xia Weng, Chengyin Fang, Xisheng Li, Baoxiu Cao, Xiaofei Mao, Haibo Wang, Lina Guan, Mingmei Wang, Wei Liu, Guolong |
author_sort | Lu, Lin |
collection | PubMed |
description | BACKGROUND: MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of miR-148b in regulating tumor progression remain unclear. METHODS: Firstly animal experiments were performed to verify whether miR-148b could inhibit the tumor growth. Then, the underlying mechanisms were studied by transfecting recombinant plasmids containing a miR-148b mimic or a negative control (NC) mimic (shRNA control) into NSCLC cell lines PC14/B and A549 cells. Tumor cells transfected with unpackaged lentiviral vectors was used as blank control. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. Cell cycle arrest was compared to clarify the mechanism underlying the tumor cell proliferation. Annexin V-FITC Apoptosis Detection kit was applied to investigate the effect of miR-148b on cell apoptosis. Furthermore, western blot analysis were performed to study the targeting pathway. RESULTS: We found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiment showed that miR-148b inhibited tumor cell proliferation. Besides, over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing NSCLC cells from entering the mitotic phase and enhanced tumor cell apoptosis. Further western blot analysis indicated that miR148b could inhibit mitogen-activated protein kinase/Jun N-terminal kinase (MAPK/JNK) signaling by decreasing the expression of phosphorylated (p) JNK. CONCLUSIONS: These results demonstrate that miR-148b could inhibit the tumor growth and act as tumor suppressor by inhibiting the proliferation and inducing apoptosis of NSCLC cells by blocking the MAPK/JNK pathway. |
format | Online Article Text |
id | pubmed-6408859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64088592019-03-21 MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway Lu, Lin Liu, Qiyao Wang, Peipei Wu, Yong Liu, Xia Weng, Chengyin Fang, Xisheng Li, Baoxiu Cao, Xiaofei Mao, Haibo Wang, Lina Guan, Mingmei Wang, Wei Liu, Guolong BMC Cancer Research Article BACKGROUND: MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of miR-148b in regulating tumor progression remain unclear. METHODS: Firstly animal experiments were performed to verify whether miR-148b could inhibit the tumor growth. Then, the underlying mechanisms were studied by transfecting recombinant plasmids containing a miR-148b mimic or a negative control (NC) mimic (shRNA control) into NSCLC cell lines PC14/B and A549 cells. Tumor cells transfected with unpackaged lentiviral vectors was used as blank control. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. Cell cycle arrest was compared to clarify the mechanism underlying the tumor cell proliferation. Annexin V-FITC Apoptosis Detection kit was applied to investigate the effect of miR-148b on cell apoptosis. Furthermore, western blot analysis were performed to study the targeting pathway. RESULTS: We found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiment showed that miR-148b inhibited tumor cell proliferation. Besides, over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing NSCLC cells from entering the mitotic phase and enhanced tumor cell apoptosis. Further western blot analysis indicated that miR148b could inhibit mitogen-activated protein kinase/Jun N-terminal kinase (MAPK/JNK) signaling by decreasing the expression of phosphorylated (p) JNK. CONCLUSIONS: These results demonstrate that miR-148b could inhibit the tumor growth and act as tumor suppressor by inhibiting the proliferation and inducing apoptosis of NSCLC cells by blocking the MAPK/JNK pathway. BioMed Central 2019-03-08 /pmc/articles/PMC6408859/ /pubmed/30849960 http://dx.doi.org/10.1186/s12885-019-5400-3 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Lu, Lin Liu, Qiyao Wang, Peipei Wu, Yong Liu, Xia Weng, Chengyin Fang, Xisheng Li, Baoxiu Cao, Xiaofei Mao, Haibo Wang, Lina Guan, Mingmei Wang, Wei Liu, Guolong MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway |
title | MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway |
title_full | MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway |
title_fullStr | MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway |
title_full_unstemmed | MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway |
title_short | MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway |
title_sort | microrna-148b regulates tumor growth of non-small cell lung cancer through targeting mapk/jnk pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408859/ https://www.ncbi.nlm.nih.gov/pubmed/30849960 http://dx.doi.org/10.1186/s12885-019-5400-3 |
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