miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells.
Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in the development and progression of various types of cancers. However, its role in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this study was to investigate the contribution of miR-146a to v...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/5afe555df6d7441d85d1f9ee2a956a74 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:5afe555df6d7441d85d1f9ee2a956a74 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:5afe555df6d7441d85d1f9ee2a956a742021-11-18T07:51:52ZmiR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells.1932-620310.1371/journal.pone.0060317https://doaj.org/article/5afe555df6d7441d85d1f9ee2a956a742013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555954/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in the development and progression of various types of cancers. However, its role in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this study was to investigate the contribution of miR-146a to various aspects of the malignant phenotype of human NSCLCs. In functional experiments, miR-146a suppressed cell growth, induced cellular apoptosis and inhibited EGFR downstream signaling in five NSCLC cell lines (H358, H1650, H1975, HCC827 and H292). miR-146a also inhibited the migratory capacity of these NSCLC cells. On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab). These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR. Our results suggest that these effects of miR-146a are due to its targeting of EGFR and NF-κB signaling. We also found, in clinical formalin fixed paraffin embedded (FFPE) lung cancer samples, that low expression of miR-146a was correlated with advanced clinical TNM stages and distant metastasis in NSCLC (P<0.05). The patients with high miR-146a expression in their tumors showed longer progression-free survival (25.6 weeks in miR-146a high patients vs. 4.8 weeks in miR-146a low patients, P<0.05). miR-146a is therefore a strong candidate prognostic biomarker in NSCLC. Thus inducing miR-146a might be a therapeutic strategy for NSCLC.Gang ChenIjeoma Adaku UmeloShasha LvErik TeugelsKarel FostierPeter KronenbergerAlex DewaeleJan SadonesCaroline GeersJacques De GrèvePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e60317 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Gang Chen Ijeoma Adaku Umelo Shasha Lv Erik Teugels Karel Fostier Peter Kronenberger Alex Dewaele Jan Sadones Caroline Geers Jacques De Grève miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. |
| description |
Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in the development and progression of various types of cancers. However, its role in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this study was to investigate the contribution of miR-146a to various aspects of the malignant phenotype of human NSCLCs. In functional experiments, miR-146a suppressed cell growth, induced cellular apoptosis and inhibited EGFR downstream signaling in five NSCLC cell lines (H358, H1650, H1975, HCC827 and H292). miR-146a also inhibited the migratory capacity of these NSCLC cells. On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab). These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR. Our results suggest that these effects of miR-146a are due to its targeting of EGFR and NF-κB signaling. We also found, in clinical formalin fixed paraffin embedded (FFPE) lung cancer samples, that low expression of miR-146a was correlated with advanced clinical TNM stages and distant metastasis in NSCLC (P<0.05). The patients with high miR-146a expression in their tumors showed longer progression-free survival (25.6 weeks in miR-146a high patients vs. 4.8 weeks in miR-146a low patients, P<0.05). miR-146a is therefore a strong candidate prognostic biomarker in NSCLC. Thus inducing miR-146a might be a therapeutic strategy for NSCLC. |
| format |
article |
| author |
Gang Chen Ijeoma Adaku Umelo Shasha Lv Erik Teugels Karel Fostier Peter Kronenberger Alex Dewaele Jan Sadones Caroline Geers Jacques De Grève |
| author_facet |
Gang Chen Ijeoma Adaku Umelo Shasha Lv Erik Teugels Karel Fostier Peter Kronenberger Alex Dewaele Jan Sadones Caroline Geers Jacques De Grève |
| author_sort |
Gang Chen |
| title |
miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. |
| title_short |
miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. |
| title_full |
miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. |
| title_fullStr |
miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. |
| title_full_unstemmed |
miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. |
| title_sort |
mir-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/5afe555df6d7441d85d1f9ee2a956a74 |
| work_keys_str_mv |
AT gangchen mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT ijeomaadakuumelo mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT shashalv mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT erikteugels mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT karelfostier mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT peterkronenberger mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT alexdewaele mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT jansadones mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT carolinegeers mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells AT jacquesdegreve mir146ainhibitscellgrowthcellmigrationandinducesapoptosisinnonsmallcelllungcancercells |
| _version_ |
1718422853176524800 |