TY - JOUR

T1 - Effects of Endocrine Disruptors o,p′-Dichlorodiphenyltrichloroethane, p,p′-Dichlorodiphenyltrichloroethane, and Endosulfan on the Expression of Estradiol-, Progesterone-, and Testosterone-Responsive MicroRNAs and Their Target Genes in MCF-7 Cells

AU - Kalinina, Tatiana

AU - Kononchuk, Vladislav

AU - Klyushova, Lyubov

AU - Gulyaeva, Lyudmila

N1 - Funding Information: Funding: This work was supported by the Russian Science Foundation, grant number 19-15-00319. Funding Information: Acknowledgments: The work was performed using the equipment of the Multi-Access Center “Proteomic Analysis,” supported by funding from the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-15-2021-691). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/1

Y1 - 2022/1

N2 - Many studies have shown that dichlorodiphenyltrichloroethane (DDT) exposure raises breast cancer risk. Another insecticide with similar properties is endosulfan, which has been ac-tively used in agriculture after DDT prohibition. Previously, we have identified some estradiol-, progesterone-, and testosterone-sensitive microRNAs (miRNAs, miRs). Because DDT and endosulfan have estrogenic, antiandrogenic, and antiprogesterone properties, we hypothesized that these miR-NAs are affected by the insecticides. We quantified relative levels of miRNAs and expression levels of their target genes in breast cancer MCF-7 cells treated with p,p′-DDT, o,p′-DDT, or endosulfan. We also quantified miR-19b expression, which, as previously shown, is regulated by estrogen. Here, we observed that miR-19b expression increased in response not only to estradiol but also to testosterone and progesterone. Treatment of MCF-7 cells with p,p′-DDT or endosulfan decreased the protein levels of apoptosis regulators TP53INP1 and APAF1. In cells treated with o,p′-DDT, the TP53INP1 amount decreased after 24 h of incubation, but increased after 48 h of incubation with insecticide. OXTR expression, which is known to be associated with breast carcinogenesis, significantly diminished under the exposure of all insecticides. In cells treated with p,p′-DDT or o,p′-DDT, the observed changes were accompanied by alterations of the levels of hormone-responsive miRNAs: miR-324, miR-190a, miR-190b, miR-27a, miR-193b, and miR-19b.

AB - Many studies have shown that dichlorodiphenyltrichloroethane (DDT) exposure raises breast cancer risk. Another insecticide with similar properties is endosulfan, which has been ac-tively used in agriculture after DDT prohibition. Previously, we have identified some estradiol-, progesterone-, and testosterone-sensitive microRNAs (miRNAs, miRs). Because DDT and endosulfan have estrogenic, antiandrogenic, and antiprogesterone properties, we hypothesized that these miR-NAs are affected by the insecticides. We quantified relative levels of miRNAs and expression levels of their target genes in breast cancer MCF-7 cells treated with p,p′-DDT, o,p′-DDT, or endosulfan. We also quantified miR-19b expression, which, as previously shown, is regulated by estrogen. Here, we observed that miR-19b expression increased in response not only to estradiol but also to testosterone and progesterone. Treatment of MCF-7 cells with p,p′-DDT or endosulfan decreased the protein levels of apoptosis regulators TP53INP1 and APAF1. In cells treated with o,p′-DDT, the TP53INP1 amount decreased after 24 h of incubation, but increased after 48 h of incubation with insecticide. OXTR expression, which is known to be associated with breast carcinogenesis, significantly diminished under the exposure of all insecticides. In cells treated with p,p′-DDT or o,p′-DDT, the observed changes were accompanied by alterations of the levels of hormone-responsive miRNAs: miR-324, miR-190a, miR-190b, miR-27a, miR-193b, and miR-19b.

KW - Dichlorodiphenyltrichloroethane

KW - Endocrine disruptor

KW - Endosulfan

KW - Hormone receptor

KW - MicroRNA

KW - Organochlorine pesticide

UR - http://www.scopus.com/inward/record.url?scp=85123550524&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/c18f1ecf-8b70-33a8-b415-31c0f42b2f3c/

U2 - 10.3390/toxics10010025

DO - 10.3390/toxics10010025

M3 - Article

C2 - 35051067

AN - SCOPUS:85123550524

VL - 10

JO - Toxics

JF - Toxics

SN - 2305-6304

IS - 1

M1 - 25

ER -