miR526b and miR655 Induce Oxidative Stress in Breast Cancer

Autor: Braydon Nault, Sujit Maiti, Kingsley Chukwunonso Ugwuagbo, Riley Feser, Mousumi Majumder, Stephanie Hunter, Bonita Shin
Rok vydání: 2019
Předmět:
medicine.disease_cause
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
superoxide (SO)
lcsh:QH301-705.5
Spectroscopy
chemistry.chemical_classification
0303 health sciences
Superoxide
General Medicine
3. Good health
Computer Science Applications
Gene Expression Regulation
Neoplastic
miR526b
030220 oncology & carcinogenesis
MCF-7 Cells
Female
medicine.symptom
Inflammation
Breast Neoplasms
reactive oxygen species (ROS)
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Breast cancer
breast cancer
Downregulation and upregulation
microRNA
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
030304 developmental biology
Reactive oxygen species
Organic Chemistry
Cancer
medicine.disease
miR655
Thioredoxin Reductase 1 (TXNRD1)
MicroRNAs
Oxidative Stress
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Cancer research
MicroRNA (miRNA)
Reactive Oxygen Species
Oxidative stress
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 20, Iss 16, p 4039 (2019)
Volume 20
Issue 16
ISSN: 1422-0067
Popis: In eukaryotes, overproduction of reactive oxygen species (ROS) causes oxidative stress, which contributes to chronic inflammation and cancer. MicroRNAs (miRNAs) are small, endogenously produced RNAs that play a major role in cancer progression. We established that overexpression of miR526b/miR655 promotes aggressive breast cancer phenotypes. Here, we investigated the roles of miR526b/miR655 in oxidative stress in breast cancer using in vitro and in silico assays. miRNA-overexpression in MCF7 cells directly enhances ROS and superoxide (SO) production, detected with fluorescence assays. We found that cell-free conditioned media contain extracellular miR526b/miR655 and treatment with these miRNA-conditioned media causes overproduction of ROS/SO in MCF7 and primary cells (HUVECs). Thioredoxin Reductase 1 (TXNRD1) is an oxidoreductase that maintains ROS/SO concentration. Overexpression of TXNRD1 is associated with breast cancer progression. We observed that miR526b/miR655 overexpression upregulates TXNRD1 expression in MCF7 cells, and treatment with miRNA-conditioned media upregulates TXNRD1 in both MCF7 and HUVECs. Bioinformatic analysis identifies two negative regulators of TXNRD1, TCF21 and PBRM1, as direct targets of miR526b/miR655. We validated that TCF21 and PBRM1 were significantly downregulated with miRNA upregulation, establishing a link between miR526b/miR655 and TXNRD1. Finally, treatments with oxidative stress inducers such as H2O2 or miRNA-conditioned media showed an upregulation of miR526b/miR655 expression in MCF7 cells, indicating that oxidative stress also induces miRNA overexpression. This study establishes the dynamic functions of miR526b/miR655 in oxidative stress induction in breast cancer.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje