Clinical significance of miR-26a-5p-regulated MCL-1 expression in preeclampsia
YANG ying1, GOU Wen-li2, GU Yin1, CHENG Li1, LAI Cai-qin1, JU Ye-Lan1, WANG Chen-hong1
1. Shenzhen Maternal and Child Health Hospital, Guangzhou Medical University, Shenzhen 518000, China;
2. The First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710000, China
AIM: To investigate the clinical significance of microRNA-26a-5p (miR-26a-5p)-regulated myeloid cell leukemia-1 (MCL-1) expression in the development of maternal preeclampsia.METHODS: Plasma and placental tissues were collected from 21 cases of normal pregnancy, 13 cases of maternal gestational hypertension, 15 cases of mild preeclampsia and 26 cases of severe preeclampsia. The levels of plasma and placental miR-26a-5p and placental MCL-1 mRNA were detected by real-time PCR. Western blotting analysis was used to determine the protein expression of placental MCL-1. The clinical significance of the above parameters was also analyzed.RESULTS: miR-26a-5p expression gradually increased(P<0.01) in the 4 groups of maternal plasma and placentas with the disease development, and the mRNA expression of MCL-1 was significantly reduced in the placentas (P<0.01), both showing a significant negative correlation (P<0.01). Meanwhile, the expression of miR-26a-5p and MCL-1 protein in the placental tissues was negatively correlated (P<0.01). The miR-26a-5p up-regulation in maternal plasma and placental tissues was negatively correlated with gestational age, maternal plasma albumin levels and fetal weight, while it was positively correlated with maternal blood pressure and urinary protein level (P<0.01), which was in contrary to the down-regulation of placental MCL-1.CONCLUSION: Up-regulation of miR-26a-5p is involved in the occurrence and development of preeclampsia by down-regulation of MCL-1.
Kanasaki K, Kalluri R. The biology of preeclampsia[J]. Kidney Int, 2009, 76(8):831-837.
[2]
Enquobahrie DA, Abetew DF, Sorensen TK, et al. Placental microRNA expression in pregnancies complicated by preeclampsia[J]. Am J Obstet Gynecol, 2011, 204(2):178.e12-178.e21.
[3]
Pineles BL, Romero R, Montenegro D, et al. Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia[J]. Am J Obstet Gynecol, 2007, 196(3):261.e1-261.e6.
[4]
Hu Y, Li P, Hao S, et al. Differential expression of microRNAs in the placentae of Chinese patients with severe pre-eclampsia[J]. Clin Chem Lab Med, 2009, 47(8):923-929.
[5]
Hromadnikova I, Kotlabová K, Jirásek JE, et al. Detection of placenta-specific microRNAs in maternal circulation[J]. Ceska Gynekol, 2010, 75(3):252-256.
[6]
Mayor-Lynn K, Toloubeydokhti T, Cruz AC, et al. Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor[J]. Reprod Sci, 2011, 18(1):46-56.
[7]
Wu L, Zhou H, Lin H, et al. Circulating microRNAs are elevated in plasma from severe preeclamptic pregnancies[J]. Reproduction, 2012, 143(3):389-397.
[8]
Choi SY, Yun J, Lee OJ, et al. MicroRNA expression profiles in placenta with severe preeclampsia using a PNA-based microarray[J]. Placenta, 2013, 34(9):799-804.
[9]
Yang X, Liang L, Zhang XF, et al. MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting interleukin-6-Stat3 pathway[J]. Hepatology, 2013, 58(1):158-170.
[10]
Gao J, Li L, Wu M, et al. MiR-26a inhibits proliferation and migration of breast cancer through repression of MCL-1[J]. PLoS One, 2013, 8(6):e65138.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method[J]. Methods, 2001, 25(4):402-408.
Soleymanlou N, Jurisicova A, Wu Y, et al. Hypoxic switch in mitochondrial myeloid cell leukemia factor-1/Mtd apoptotic rheostat contributes to human trophoblast cell death in preeclampsia[J]. Am J Pathol, 2007, 171(2):496-506.
[15]
Kalkat M, Garcia J, Ebrahimi J, et al. Placental auto-phagy regulation by the BOK-MCL1 rheostat[J]. Auto-phagy, 2013, 9(12):2140-2153.
[16]
Gong JS, Kim GJ. The role of autophagy in the placenta as a regulator of cell death[J]. Clin Exp Reprod Med, 2014, 41(3):97-107.
[17]
Bai Y, Wang L, Sun L, et al. Circulating microRNA-26a:potential predictors and therapeutic targets for non-hypertensive intracerebral hemorrhage[J]. Med Hypotheses, 2011, 77(4):488-490.
[18]
Ho J, Ng KH, Rosen S, et al. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury[J]. J Am Soc Nephrol, 2008, 19(11):2069-2075.