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MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer
- Source :
- Oncotarget 8 (2017): 19507–19521. doi:10.18632/oncotarget.14470, info:cnr-pdr/source/autori:Roscigno G.; Puoti I.; Giordano I.; Donnarumma E.; Russo V.; Affinito A.; Adamo A.; Quintavalle C.; Todaro M.; Vivanco M.D.; Condorelli G./titolo:MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer/doi:10.18632%2Foncotarget.14470/rivista:Oncotarget/anno:2017/pagina_da:19507/pagina_a:19521/intervallo_pagine:19507–19521/volume:8, Oncotarget
- Publication Year :
- 2017
- Publisher :
- Impact Journals, Albany, N.Y. , Stati Uniti d'America, 2017.
-
Abstract
- // Giuseppina Roscigno 1, 2, * , Ilaria Puoti 1, 2, * , Immacolata Giordano 1 , Elvira Donnarumma 3 , Valentina Russo 1 , Alessandra Affinito 1 , Assunta Adamo 1 , Cristina Quintavalle 1, 2 , Matilde Todaro 4 , Maria dM Vivanco 5 , Gerolama Condorelli 1, 2 1 Department of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, Italy 2 IEOS, CNR, Naples, Italy 3 IRCCS-SDN, Naples, Italy 4 Department of Pathobiology and Medical Biotechnology, University of Palermo, Palermo, Italy 5 CIC bioGUNE, Centre for Cooperative Research in Biosciences, Derio, Spain * These authors have contributed equally to the paper as first authors Correspondence to: Gerolama Condorelli, email: gecondor@unina.it Keywords: microRNAs, breast cancer, cancer stem cells, BimL, FIH1 Received: May 17, 2016 Accepted: November 30, 2016 Published: January 03, 2017 ABSTRACT Breast cancer remains one of the leading causes of cancer mortality among women. It has been proved that the onset of cancer depends on a very small pool of tumor cells with a phenotype similar to that of normal adult stem cells. Cancer stem cells (CSC) possess self-renewal and multilineage differentiation potential as well as a robust ability to sustain tumorigenesis. Evidence suggests that CSCs contribute to chemotherapy resistance and to survival under hypoxic conditions. Interestingly, hypoxia in turn regulates self-renewal in CSCs and these effects may be primarily mediated by hypoxic inducible factors (HIFs). Recently, microRNAs (miRNAs) have emerged as critical players in the maintenance of pluripotency and self-renewal in normal and cancer stem cells. Here, we demonstrate that miR-24 is upregulated in breast CSCs and that its overexpression increases the number of mammospheres and the expression of stem cell markers. MiR-24 also induces apoptosis resistance through the regulation of BimL expression. Moreover, we identify a new miR-24 target, FIH1, which promotes HIFα degradation: miR-24 increases under hypoxic conditions, causing downregulation of FIH1 and upregulation of HIF1α. In conclusion, miR-24 hampers chemotherapy-induced apoptosis in breast CSCs and increases cell resistance to hypoxic conditions through an FIH1−HIFα pathway.
- Subjects :
- 0301 basic medicine
cancer stem cells
Apoptosis
Stem cell marker
medicine.disease_cause
microRNAs, Breast cancer, Cancer stem cells, BimL, FIH1
Mixed Function Oxygenases
Antineoplastic Agent
0302 clinical medicine
Cell Movement
Tumor Cells, Cultured
Cell Self Renewal
Mixed Function Oxygenase
BimL
microRNA
Cell Hypoxia
microRNAs
Gene Expression Regulation, Neoplastic
Oncology
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Female
Breast Neoplasm
Adult stem cell
Human
Research Paper
FIH1
breast cancer
Antineoplastic Agents
Breast Neoplasms
03 medical and health sciences
Breast cancer
Downregulation and upregulation
Cancer stem cell
medicine
Biomarkers, Tumor
Humans
Cell Proliferation
business.industry
Apoptosi
Repressor Protein
medicine.disease
Hypoxia-Inducible Factor 1, alpha Subunit
Molecular medicine
Repressor Proteins
030104 developmental biology
Drug Resistance, Neoplasm
Immunology
Cancer research
Neoplastic Stem Cell
Cisplatin
Carcinogenesis
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Oncotarget 8 (2017): 19507–19521. doi:10.18632/oncotarget.14470, info:cnr-pdr/source/autori:Roscigno G.; Puoti I.; Giordano I.; Donnarumma E.; Russo V.; Affinito A.; Adamo A.; Quintavalle C.; Todaro M.; Vivanco M.D.; Condorelli G./titolo:MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer/doi:10.18632%2Foncotarget.14470/rivista:Oncotarget/anno:2017/pagina_da:19507/pagina_a:19521/intervallo_pagine:19507–19521/volume:8, Oncotarget
- Accession number :
- edsair.doi.dedup.....bbe34e298798207e797a9f8304dc08a1