بررسی میزان بیان miR200a به‌عنوان یک بیومارکر در زنان مبتلا به زایمان زودرس

نوع مقاله : اصیل پژوهشی

نویسندگان

1 کارشناس ارشد گروه ژنتیک، دانشکده علوم و فناوری‌های نوین، علوم پزشکی تهران، دانشگاه آزاد اسلامی، تهران، ایران.

2 استادیار گروه زنان و مامایی، فلوشیپ پریناتولوژی گروه زنان و زایمان، دانشکده پزشکی، دانشگاه علوم پزشکی اردبیل، اردبیل، ایران.

3 استادیار گروه ژنتیک، دانشکده علوم و فناوری‌های نوین، علوم پزشکی تهران، دانشگاه آزاد اسلامی، تهران، ایران.

4 دانشیار گروه ژنتیک پزشکی، دانشکده پزشکی، دانشگاه علوم پزشکی اردبیل، اردبیل، ایران

چکیده

مقدمه: زایمان زودرس، یکی از مشکلات اصلی بهداشتی محسوب می‌شود و بعد از ناهنجاری‌های مادرزادی، اصلی‌ترین عامل ابتلاء به بیماری و مرگ‌ومیر نوزادان است. با توجه به نقش گسترده MicroRNA‌ها به‌عنوان بیومارکر در تشخیص انواع بیماری‌ها، مطالعه حاضر با هدف بررسی میزان بیان miR200a به‌عنوان یک بیومارکر در زنان مبتلا به زایمان زودرس در استان اردبیل انجام شد.
روش‌کار: این مطالعه مورد شاهدی از مهر 1396 تا آذر 1397 بر روی 50 زن باردار نخست باردار سالم و 50 زن نخست باردار که برای زایمان زودرس به بیمارستان علوی شهر اردبیل مراجعه کرده بودند، انجام شد. پس از استخراج MicroRNA از خون و سنتز cDNA به‌منظور بررسی میزان بیان miR200a از تکنیک Real Time PCR استفاده شد. تجزیه و تحلیل داده‌ها با استفاده از نرم‌افزار آماری SPSS (نسخه 20) و آزمون آنوا، وان وی و تی تست انجام شد. میزان p کمتر از 05/0 معنادار در نظر گرفته شد.
یافته‌ها: میزان بیان miR200a در گروه نرمال 04/0±35/0 و در گروه زایمان زودرس 09/0±24/0 بود که نسبت به گروه نرمال بارداری، به میزان 11% کاهش بیان داشت. همچنین اختصاصیت و حساسیت انجام این تست برای بررسی زایمان زودرس به‌ترتیب برابر 4/53% و 74% بود که توسط منحنی ROC مورد بررسی قرار گرفت. این نتایج از نظر آماری معنادار بود (05/0≥p).
نتیجه‌گیری: در این پژوهش میزان بیان microRNA200a مورد مطالعه در بین زنان با زایمان زودرس و طبیعی متفاوت بود و به‌نظر می‌رسد، بتوان از miR200a به‌عنوان یک بیومارکر جدید برای پیش‌بینی زایمان زودرس استفاده کرد.

کلیدواژه‌ها


عنوان مقاله [English]

Expression of miR200a as a biomarker in women with preterm delivery

نویسندگان [English]

  • Effat Seyed Hashemi 1
  • Roghaye Dargahi 2
  • Malihe Entezari 3
  • Seyed Saeed l Hosseini As 4
1 M.Sc. of Genetics, School of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
2 Assistant professor, Department of Obstetrics and Gynecology, Fellowship of Perinatology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
3 Assistant professor, Department of Genetics, School of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
4 Associate professor, Department of Medical Genetics, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
چکیده [English]

Introduction: Preterm delivery is one of the main health problems and after congenital anomalies is the main cause of neonatal disease and mortality. Considering the main role of microRNAs as Biomarkers in the diagnosis of various types of diseases, this study was performed with aim to investigate the expression of miR200a as a biomarker in women with preterm delivery in Ardabil province.
Methods: This case-control study was performed on 50 healthy nulliparous women and 50 nulliparous women who had referred to Ardabil Alavi hospital for preterm labor from October 2017 to December 2018. After extracting MicroRNA and synthesis of cDNA, real time PCR technique was used to determine miR200a expression. Data were analyzed by SPSS software (version 20) and ANOVA, t-test, and v-one test. P<0.05 was considered statistically significant.
Results: The expression of miR200a in the normal group was 0.35±0.04, and in the preterm delivery group was 0.24± 0.09 that had 11% decreases in expression compared to the healthy group. Also, specificity and sensitivity of this test for evaluation of preterm delivery was 53.4% and 74%, respectively, which was assessed by ROC curve. These results were statistically significant (P ≤ 0.05).
Conclusion: The expression of microRNA200a as a Biomarker was different among normal pregnant women and those with preterm delivery; it seems that microRNA200a can be used as a new marker to predict preterm delivery.

کلیدواژه‌ها [English]

  • Biomarker
  • microRNA
  • Preterm delivery
  1. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2017; 3:CD004454.
  2. Cunningham L, Bloom H, Rouse S. Williams obstetrics. Trans: Voladan M, Razzaghi S, Ghorbani MH. Tehran: Arjmand Press; 2010. (Persian).
  3. Sohrabi D, Ghanbari Gorgani M. Study of risk factors during pregnancy on preterm birth in women-ValiAsr Hospital Zanjan-2007. J Urmia Nurs Midwifery Sch 2011; 9(2):93. (Persian).
  4. Sharma AJ, Vesco KK, Bulkley J, Callaghan WM, Bruce FC, Staab J, et al. Rate of second and third trimester weight gain and preterm delivery among underweight and normal weight women. Matern Child Health J 2016; 20(10):2030-6.
  5. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008; 371(9606):75-84.
  6. Shoja M, Shoja E, Gharaei M. Prevalence and affecting factors on preterm birth in pregnant women Referred to Bentolhoda hospital-Bojnurd. J North Khorasan Univ Med Sci 2016; 7(4):855-63. (Persian).
  7. Davari Tanha F, Valadan M, Kave M, Bagher Zadeh Jalilvands HM. Prevalence and risk factors of recurrent preterm delivery in three hospitals of Tehran University. J Tehran Univ Med Sci 2007; 65(2):34-9. (Persian).
  8. Najar S, Sharafi F, Afshari P, HaghighizadehMH. The relationship between sleep disorders during pregnancy and premature labor and low birth weight. Iran J Obstet Gynecol Infertil 2017; 20(7):44-9. (Persian).
  9. Rieder TN. Saving or creating: which are we doing when we resuscitate extremely preterm infants? Am J Bioeth 2017; 17(8):4-12.
  10. Elovitz MA, Brown AG, Anton L, Gilstrop M, Heiser L, Bastek J. Distinct cervical microRNA profiles are present in women destined to have a preterm birth. Am J Obstet Gynecol 2014; 210(3):221.e1-11.
  11. Lucas K, Raikhel AS. Insect microRNAs: biogenesis, expression profiling and biological functions. Insect Biochem Mol Biol 2013; 43(1):29-38.
  12. Dargahi D, Shahbazzadegan S, Naghizadeh-BaghiA, Sefati Kooyakhi S. Expression levels of drosha and dicer enzymes and DGCR8 protein in pre-eclamptic patients. Iran J Obstet Gynecol Infertil 2018; 20(12):40-9. (Persian).
  13. Nagy Z, Igaz P. Introduction to microRNAs: biogenesis, action, relevance of tissue micrornas in disease pathogenesis, diagnosis and therapy-the concept of circulating microRNAs. Exp Suppl 2015; 106:3-30.
  14. Pineles BL, Romero R, Montenegro D, Tarca AL, Han YM, Kim YM, et al. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia. Am J Obstet Gynecol 2007; 196(3):261.e1-6.
  15. Williams KC, Renthal NE, Condon JC, Gerard RD, Mendelson CR. MicroRNA-200a serves a key role in the decline of progesterone receptor function leading to term and preterm labor. Proc Natl Acad Sci 2012; 109(19):7529-34.
  16. Ming J, Zhou Y, Du J, Fan S, Pan B, Wang Y, et al. Identification of miR-200a as a novel suppressor of connexin 43 in breast cancer cells. Biosci Rep 2015; 35(5):e00251.
  17. Brind J, Condly SJ, Lanfranci A, Rooney B. Induced abortion as an independent risk factor for breast cancer: a systematic review and meta-analysis of studies on south asian women. Issues Law Med 2018; 33(1):33-54.
  18. Hassan SS, Romero R, Pineles B, Tarca AL, Montenegro D, Erez O, et al. MicroRNA expression profiling of the human uterine cervix after term labor and delivery. Am J Obstet Gynecol 2010; 202(1):80.e1-8.
  19. Sanders AP, Burris HH, Just AC, Motta V, Svensson K, Mercado-Garcia A, et al. microRNA expression in the cervix during pregnancy is associated with length of gestation. Epigenetics 2015; 10(3):221-8.
  20. Zhao Z, Moley KH, Gronowski AM. Diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases. Clin Biochem 2013; 46(10-11):953-60.
  21. Winger EE, Reed JL, Ji X. Early first trimester peripheral blood cell microRNA predicts risk of preterm delivery in pregnant women: proof of concept. PloS One 2017; 12(7):e0180124.
  22. Pan Q, Luo X, Toloubeydokhti T, Chegini N. The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression. Mol Hum Reprod 2007; 13(11):797-806.
  23. Murphy MS, Casselman RC, Tayade C, Smith GN. Differential expression of plasma microRNA in preeclamptic patients at delivery and 1 year postpartum. Am J Obstet Gynecol 2015; 213(3):367.e1-9.
  24. Liu Y, Sánchez-Tilló E, Lu X, Huang L, Clem B, Telang S, et al. The ZEB1 transcription factor acts in a negative feedback loop with miR200 downstream of Ras and Rb1 to regulate Bmi1 expression. J Biol Chem 2014; 289(7):4116-25.
  25. Williams Kr. Antagonistic roles of miR-199a-3p/miR-214 and the miR-200 family in the regulation of uterine contractility during pregnancy and labor. Texas: UT Southwestern Graduate School of Biomedical Sciences; 2014.
  26. Renthal NE, Chen CC, Williams KC, Gerard RD, Prange-Kiel J, Mendelson CR. miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proc Natl Acad Sci U S A 2010; 107(48):20828-33.
  27. Milunsky A, Baldwin C, Milunsky J. Molecular genetics and prenatal diagnosis. genetic disorders and the fetus. New Jersey: Wiley-Blackwell; 2015. P. 380-418.
  28. Wang Y, Yang X, Yang Y, Wang W, Zhao M, Liu H, et al. High-throughput deep screening and identification of four peripheral leucocyte microRNAs as novel potential combination biomarkers for preeclampsia. J Perinatol 2016; 36(4):263-7.
  29. Giarratano G. Genetic influences on preterm birth. MCN Am J Matern Child Nurs 2006; 31(3):169-75.
  30. Gilbert JS, Nijland MJ, Knoblich P. Placental ischemia and cardiovascular dysfunction in preeclampsia and beyond: making the connections. Expert Rev Cardiovasc Ther 2008; 6(10):1367-77.