Identification of preeclampsia-related miRNA by a deep sequencing technique and a real-time quantitative PCR


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Abstract

Objective. To comparatively analyze the miRNA expression profile in the placental and peripheral plasma samples from pregnant women with physiological pregnancy and preeclampsia. Material and methods. The investigators used a miRNA deep sequencing technique (HiSeq 2000, Illumina) in the placental and plasma samples from apparently healthy women and pregnant women with early and late preeclampsia and then validated the findings by a real-time quantitative PCR assay (StepOnePlus™). Results. There was a significant decrease in the expression of hsa-miR-532-5p, -423-5p, -127-3p, -376a-5p, -539-5p, and -519a-3p in the placenta and a significant increase in that of hsa-miR-423-5p and -519a-3p in the plasma of pregnant women with preeclampsia by more than twice. An association was first found between the change in the expression of the above miRNAs and the presence of preeclampsia in pregnant women, exclusive of miR-519a-3p, the changed transcriptional profile of which had been already demonstrated in preeclampsia. The application of the logistic regression model constructed using the data of the investigations showed that the risk of early preeclampsia increased with higher miR-423-5p expression levels in the plasma of pregnant women. This observation may become the basis for the testing system through screening pregnant women for the early diagnosis of preeclampsia until the disease shows its clinical manifestation. Conclusion. The found miRNAs are potentially regulators of the signaling pathways that are involved in ovarian folliculogenesis and steroidogenesis; in antigen processing and presentation; in endometrial decidualization and maintenance of early pregnancy; in graft-versus-host disease; in the development of an autoimmune disease; in cell migration and invasion, in focal adhesion and regulation of the actin cytoskeleton; in intracellular calcium transport and calcium-dependent reactions; in complement activation and blood coagulation; in aldosterone-regulated sodium reabsorption; in the renin-angiotensin system, as well as in p53- and prohibitin-mediated cellular apoptosis, which is as a whole within the general notion that these signaling pathways are implicated in the pathogenesis of preeclampsia.

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About the authors

Angelica V. Timofeeva

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: avtimofeeva28@gmail.com
PhD, senior researcher at the Laboratory of Molecular Pathophysiology Department of Systems Biology in reproduction

Vladislav A. Gusar

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: v_gusar@mail.ru
Ph.D., senior researcher at the Laboratory of Molecular Pathophysiology Department of Systems Biology in reproduction

Kseniya N. Prozorovskaya

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: ksenyap@inbox.ru
obstetrician-gynecologist of observational obstetrics department

Ivan S. Balashov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: i_balashov@oparina4.ru
specialist of laboratory of bioinformatics

Natalia A. Lomova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: natasha-lomova@yandex.ru
Ph.D., researcher of observational obstetric department

Maria B. Ganichkina

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: mariaganichkina@yandex.ru
postgraduate

Elrad Yu. Amiraslanov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: e_amiraslanov@oparina4.ru
PhD, researcher of observational obstetric department

Maria V. Volochaeva

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

MD, obstetrician-gynecologist, obstetric department of physiological

Natalia V. Nizyaeva

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: niziaeva@gmail.com
PhD, senior researcher at the department of pathology

Pavel I. Borovikov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: p_borovikov@oparina4.ru
Head of the Laboratory of Bioinformatics

Vladimir E. Frankevich

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
Candidate of Physical and Chemical Sciences, head of the department of systems biology in reproduction

Viktor L. Tyutyunnik

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: tioutiounnik@mail.ru
MD, head of the obstetrics department of physiological

Natalya E. Kan

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: kan-med@mail.ru
MD, head of the observational obstetrics department

Mikhail Yu. Bobrov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: mbobr@mail.ru
PhD, Head of the Laboratory of Molecular Pathophysiology, Department of Systems Biology in reproduction

Gennady T. Sukhikh

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
MD, PhD, director

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