The miR-195 Axis Regulates Chemoresistance through TUBB and Lung Cancer Progression through BIRC5

Chemoresistance and metastasis are the major reasons for non-small cell lung cancer (NSCLC) treatment failure and patient deaths. We and others have shown that miR-195 regulates the sensitivity of NSCLC to microtubule-targeting agents (MTAs) in vitro and in vivo and that miR-195 represses the migrat...

Full description

Saved in:
Bibliographic Details
Published in:Molecular therapy. Oncolytics 2019-09, Vol.14, p.288-298
Main Authors: Yu, Xiaojie, Zhang, Yiqiang, Wu, Binggen, Kurie, Jonathan M., Pertsemlidis, Alexander
Format: Article
Language:English
Subjects:
Adenocarcinoma
Binding sites
BIRC5
Breast cancer
Cancer therapies
Cell adhesion & migration
Cervical cancer
Chemoresistance
Chemotherapy
Drug resistance
Gene expression
Lung cancer
Medical prognosis
Melanoma
Metastases
Metastasis
microtubule-targeting agents
miR-195
Mutation
non-small cell lung cancer
Non-small cell lung carcinoma
Small cell lung carcinoma
Statistical analysis
Structure-function relationships
Survival analysis
TUBB
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chemoresistance and metastasis are the major reasons for non-small cell lung cancer (NSCLC) treatment failure and patient deaths. We and others have shown that miR-195 regulates the sensitivity of NSCLC to microtubule-targeting agents (MTAs) in vitro and in vivo and that miR-195 represses the migration and invasion of NSCLC cells in vitro. However, the relationship between miR-195 and microtubule structure and function and whether miR-195 represses NSCLC metastasis in vivo remain unknown. We assessed the correlation between tumor levels of TUBB and patient survival, the effect of TUBB on drug response, and the effect of miR-195 on migration, invasion, and metastasis in vitro and in vivo. We found that miR-195 directly targets TUBB; knockdown of TUBB sensitizes cells to MTAs, while overexpression confers resistance; high expression of TUBB is correlated with worse survival of lung adenocarcinoma; TUBB is also regulated by CHEK1, which has been shown to regulate chemoresistance; and miR-195 targets BIRC5 to repress migration and invasion in vitro and metastasis in vivo. Our findings highlight the relevance of the miR-195/TUBB axis in regulating the response of NSCLC to MTAs and the importance of the miR-195/BIRC5 axis in regulating NSCLC metastasis.
ISSN:2372-7705
2372-7705
DOI:10.1016/j.omto.2019.07.004