PUBLICATION
lncMat2B regulated by severe hypoxia induces cisplatin resistance by increasing DNA damage repair and tumor-initiating population in breast cancer cells
- Authors
- García-Venzor, A., Mandujano-Tinoco, E.A., Ruiz-Silvestre, A., Sánchez, J.M., Lizarraga, F., Zampedri, C., Melendez-Zajgla, J., Maldonado, V.
- ID
- ZDB-PUB-210527-13
- Date
- 2020
- Source
- Carcinogenesis 41: 1485-1497 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology
- Apoptosis
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Breast Neoplasms/drug therapy
- Breast Neoplasms/genetics
- Breast Neoplasms/metabolism
- Breast Neoplasms/pathology*
- Cell Proliferation
- Cisplatin/pharmacology*
- DNA Damage
- DNA Repair*
- Drug Resistance, Neoplasm*
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Hypoxia/physiopathology*
- Methionine Adenosyltransferase/genetics
- Neoplasm Invasiveness
- Neoplastic Stem Cells/drug effects
- Neoplastic Stem Cells/metabolism
- Neoplastic Stem Cells/pathology*
- RNA, Long Noncoding/genetics*
- Reactive Oxygen Species
- Spheroids, Cellular
- Tumor Cells, Cultured
- Tumor Microenvironment
- Zebrafish
- PubMed
- 32710610 Full text @ Carcinogenesis
Citation
García-Venzor, A., Mandujano-Tinoco, E.A., Ruiz-Silvestre, A., Sánchez, J.M., Lizarraga, F., Zampedri, C., Melendez-Zajgla, J., Maldonado, V. (2020) lncMat2B regulated by severe hypoxia induces cisplatin resistance by increasing DNA damage repair and tumor-initiating population in breast cancer cells. Carcinogenesis. 41:1485-1497.
Abstract
Multicellular tumor spheroids (MCTSs) constitute a three-dimensional culture system that recapitulates the in vivo tumor microenvironment. Tumor cells cultured as MCTSs present antineoplastic resistance due to the effect of microenvironmental signals acting upon them. In this work, we evaluated the biological function of a new microenvironment-regulated long non-coding RNA, lncMat2B, in breast cancer. In MCTSs, the expression of lncMat2B presented an increase and a zonal heterogeneity, as it was expressed principally in quiescent cells of hypoxic regions of the MCTSs. As expected, functional assays supported the role of severe hypoxia in the regulation of lncMat2B. Moreover, gain- and loss-of-function assays using a transcriptional silencing CRISPR/Cas9 system and gBlock revealed that lncMAT2B regulates the tumor-initiating phenotype. Interestingly, lncMat2B is overexpressed in a cisplatin-resistant MCF-7 cell line, and its ectopic expression in wild type MCF-7 cells increased survival to cisplatin exposure by reducing DNA damage and reactive oxygen species accumulation. lncMAT2B is a possible link between severe hypoxia, tumor-initiating phenotype and drug resistance in breast cancer cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping