Cargando…

miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer

Extensive research has suggested that miR-7 plays a critical role in cancer progression. However, the biological function of miR-7 in pancreatic cancer (PC) progression is poorly understood. Therefore, in the present study, we investigated the function of miR-7 and its molecular mechanism in PC prog...

Descripción completa

Detalles Bibliográficos
Autores principales: Xia, Jun, Cao, Tong, Ma, Cong, Shi, Ying, Sun, Yu, Wang, Z. Peter, Ma, Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171162/
https://www.ncbi.nlm.nih.gov/pubmed/30290304
http://dx.doi.org/10.1016/j.omtn.2018.08.012
_version_ 1783360739651616768
author Xia, Jun
Cao, Tong
Ma, Cong
Shi, Ying
Sun, Yu
Wang, Z. Peter
Ma, Jia
author_facet Xia, Jun
Cao, Tong
Ma, Cong
Shi, Ying
Sun, Yu
Wang, Z. Peter
Ma, Jia
author_sort Xia, Jun
collection PubMed
description Extensive research has suggested that miR-7 plays a critical role in cancer progression. However, the biological function of miR-7 in pancreatic cancer (PC) progression is poorly understood. Therefore, in the present study, we investigated the function of miR-7 and its molecular mechanism in PC progression. We used multiple methods, such as MTT, FACS, Transwell assay, RT-PCR, western blotting, and transfection to investigate the role of miR-7 in PC cells. We found that miR-7 suppressed cell growth, migration, and invasion but induced apoptosis in PC cells. Moreover, overexpression of miR-7 repressed tumor growth in mice, suggesting that miR-7 could exert its tumor-suppressive function in PC. Mechanistically, we validated that MAP3K9 is a direct target of miR-7, which significantly enhanced PC cell proliferation and inhibited cell apoptosis partly through activation of the MEK/ERK pathway and NF-κB pathway. Moreover, rescue experiments also showed that miR-7 suppressed PC cell proliferation and induced PC cell apoptosis by directly targeting MAP3K9, leading to inhibition of the MEK/ERK and NF-κB pathways. Taken together, these results suggest that miR-7/MAP3K9 is critically involved in PC progression and that miR-7 may be a potential target for PC treatment.
format Online
Article
Text
id pubmed-6171162
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher American Society of Gene & Cell Therapy
record_format MEDLINE/PubMed
spelling pubmed-61711622018-10-05 miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer Xia, Jun Cao, Tong Ma, Cong Shi, Ying Sun, Yu Wang, Z. Peter Ma, Jia Mol Ther Nucleic Acids Article Extensive research has suggested that miR-7 plays a critical role in cancer progression. However, the biological function of miR-7 in pancreatic cancer (PC) progression is poorly understood. Therefore, in the present study, we investigated the function of miR-7 and its molecular mechanism in PC progression. We used multiple methods, such as MTT, FACS, Transwell assay, RT-PCR, western blotting, and transfection to investigate the role of miR-7 in PC cells. We found that miR-7 suppressed cell growth, migration, and invasion but induced apoptosis in PC cells. Moreover, overexpression of miR-7 repressed tumor growth in mice, suggesting that miR-7 could exert its tumor-suppressive function in PC. Mechanistically, we validated that MAP3K9 is a direct target of miR-7, which significantly enhanced PC cell proliferation and inhibited cell apoptosis partly through activation of the MEK/ERK pathway and NF-κB pathway. Moreover, rescue experiments also showed that miR-7 suppressed PC cell proliferation and induced PC cell apoptosis by directly targeting MAP3K9, leading to inhibition of the MEK/ERK and NF-κB pathways. Taken together, these results suggest that miR-7/MAP3K9 is critically involved in PC progression and that miR-7 may be a potential target for PC treatment. American Society of Gene & Cell Therapy 2018-08-22 /pmc/articles/PMC6171162/ /pubmed/30290304 http://dx.doi.org/10.1016/j.omtn.2018.08.012 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Xia, Jun
Cao, Tong
Ma, Cong
Shi, Ying
Sun, Yu
Wang, Z. Peter
Ma, Jia
miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer
title miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer
title_full miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer
title_fullStr miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer
title_full_unstemmed miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer
title_short miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer
title_sort mir-7 suppresses tumor progression by directly targeting map3k9 in pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171162/
https://www.ncbi.nlm.nih.gov/pubmed/30290304
http://dx.doi.org/10.1016/j.omtn.2018.08.012
work_keys_str_mv AT xiajun mir7suppressestumorprogressionbydirectlytargetingmap3k9inpancreaticcancer
AT caotong mir7suppressestumorprogressionbydirectlytargetingmap3k9inpancreaticcancer
AT macong mir7suppressestumorprogressionbydirectlytargetingmap3k9inpancreaticcancer
AT shiying mir7suppressestumorprogressionbydirectlytargetingmap3k9inpancreaticcancer
AT sunyu mir7suppressestumorprogressionbydirectlytargetingmap3k9inpancreaticcancer
AT wangzpeter mir7suppressestumorprogressionbydirectlytargetingmap3k9inpancreaticcancer
AT majia mir7suppressestumorprogressionbydirectlytargetingmap3k9inpancreaticcancer