TY - JOUR

T1 - Associations between the levels of estradiol-, progesterone-, and testosterone-sensitive mirnas and main clinicopathologic features of breast cancer

AU - Kalinina, Tatiana

AU - Kononchuk, Vladislav

AU - Alekseenok, Efim

AU - Abdullin, Grigory

AU - Sidorov, Sergey

AU - Ovchinnikov, Vladimir

AU - Gulyaeva, Lyudmila

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

PY - 2022/1

Y1 - 2022/1

N2 - Despite the existing advances in the diagnosis and treatment of breast cancer (BC), the search for markers associated with the clinicopathological features of BC is still in demand. MiRNAs (miRs) have potential as markers, since a change in the miRNA expression profile accompanies the initiation and progression of malignant diseases. The receptors for estrogen, androgen, and progesterone (ER, AR, and PR) play an important role in breast carcinogenesis. Therefore, to search for miRNAs that may function as markers in BC, using bioinformatic analysis and the literature data, we selected 13 miRNAs whose promoter regions contain binding sites for ER or AR, or putative binding sites for ER, AR, and PR. We quantified their expression in MCF-7 cells treated with estradiol, progesterone, or testosterone. The levels of miRNAs sensitive to one or more of these hormones were quantified in BC samples (n = 196). We discovered that high expression levels of miR-190b in breast tumor tissue indicate a positive ER status, and miR-423 and miR-200b levels differ between patients with and without HER2 amplification. The miR-193b,-423,-190a,-324, and-200b levels were associated with tumor size or lymph node status in BC patients, but the presence of these associations depended on the status and expression level of ER, PR, HER2, and Ki-67. We also found that miR-21 expression depends on HER2 expression in ER-and/or PR-positive BC. The levels of miRNA were significantly different between HER2 0 and HER2 1+ tumors (p = 0.027), and between HER2 0 and HER2 2+, 3+ tumors (p = 0.005).

AB - Despite the existing advances in the diagnosis and treatment of breast cancer (BC), the search for markers associated with the clinicopathological features of BC is still in demand. MiRNAs (miRs) have potential as markers, since a change in the miRNA expression profile accompanies the initiation and progression of malignant diseases. The receptors for estrogen, androgen, and progesterone (ER, AR, and PR) play an important role in breast carcinogenesis. Therefore, to search for miRNAs that may function as markers in BC, using bioinformatic analysis and the literature data, we selected 13 miRNAs whose promoter regions contain binding sites for ER or AR, or putative binding sites for ER, AR, and PR. We quantified their expression in MCF-7 cells treated with estradiol, progesterone, or testosterone. The levels of miRNAs sensitive to one or more of these hormones were quantified in BC samples (n = 196). We discovered that high expression levels of miR-190b in breast tumor tissue indicate a positive ER status, and miR-423 and miR-200b levels differ between patients with and without HER2 amplification. The miR-193b,-423,-190a,-324, and-200b levels were associated with tumor size or lymph node status in BC patients, but the presence of these associations depended on the status and expression level of ER, PR, HER2, and Ki-67. We also found that miR-21 expression depends on HER2 expression in ER-and/or PR-positive BC. The levels of miRNA were significantly different between HER2 0 and HER2 1+ tumors (p = 0.027), and between HER2 0 and HER2 2+, 3+ tumors (p = 0.005).

KW - Biomarker

KW - Breast cancer

KW - Hormone-dependent car-cinogenesis

KW - Lymph node metastasis

KW - MicroRNA

UR - http://www.scopus.com/inward/record.url?scp=85121690450&partnerID=8YFLogxK

UR - https://www.elibrary.ru/item.asp?id=47549055

UR - https://www.mendeley.com/catalogue/5f644003-9637-36df-974f-f053f63bfdbe/

U2 - 10.3390/jpm12010004

DO - 10.3390/jpm12010004

M3 - Article

C2 - 35055320

AN - SCOPUS:85121690450

VL - 12

JO - Journal of Personalized Medicine

JF - Journal of Personalized Medicine

SN - 2075-4426

IS - 1

M1 - 4

ER -