title: MicroRNA-210 contributes to preeclampsia by downregulating potassium channel modulatory factor 1.
abstract: Preeclampsia is a pregnancy-specific syndrome manifested by the onset of hypertension and proteinuria after the 20th week of gestation. Abnormal placenta development has been generally accepted as the initial cause of the disorder. Recently, microRNA-210 (miR-210) has been found to be upregulated in preeclamptic placentas compared with normal placentas, indicating a possible association of this small molecule with the placental pathology of preeclampsia. However, the function of miR-210 in the development of the placenta remains elusive. The aim of this study was to characterize the molecular mechanism of preeclampsia development by examining the role of miR-210. In this study, miR-210 and potassium channel modulatory factor 1 (KCMF1) expressions were compared in placentas from healthy pregnant individuals and patients with preeclampsia, and the role of miR-210 in trophoblast cell invasion via the downregulation of KCMF1 was investigated in the immortal trophoblast cell line HTR8/SVneo. The levels of KCMF1 were significantly lower in preeclamptic placenta tissues than in gestational week-matched normal placentas, which was inversely correlated with the level of miR-210. KCMF1 was validated as the direct target of miR-210 using real-time polymerase chain reaction, Western blotting, and dual luciferase assay in HTR8/SVneo cells. miR-210 inhibited the invasion of trophoblast cells, and this inhibition was abrogated by the overexpression of KCMF1. The inflammatory factor tumor necrosis factor-α could upregulate miR-210 while suppressing KCMF1 expression in HTR8/SVneo cells. This is the first report on the function of KCMF1 in human placental trophoblast cells, and the data indicate that aberrant miR-210 expression may contribute to the occurrence of preeclampsia by interfering with KCMF1-mediated signaling in the human placenta.
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Rongcan
authors: R
authors: Luo
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Xuan
authors: X
authors: Shao
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Peng
authors: P
authors: Xu
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Yanlei
authors: Y
authors: Liu
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Yongqing
authors: Y
authors: Wang
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Yangyu
authors: Y
authors: Zhao
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Ming
authors: M
authors: Liu
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Lei
authors: L
authors: Ji
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Yu-Xia
authors: YX
authors: Li
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Cheng
authors: C
authors: Chang
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Jie
authors: J
authors: Qiao
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.).
authors: Chun
authors: C
authors: Peng
authors: From the State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China (R.L., X.S., P.X., Y.L., M.L., L.J., Y.-x.L., Y.-l.W.); School of Life Sciences, Lanzhou University, Lanzhou, China (R.L., C.C.); Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China (Y.W., Y.Z., J.Q.); Department of Biology, York University, Toronto, Ontario, Canada (C.P.); and University of Chinese Academy of Sciences, Beijing, China (X.S., P.X., Y.L.). wangyl@ioz.ac.cn cpeng@yorku.ca.
authors: Yan-Ling
authors: YL
authors: Wang
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics*; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; C496223:KCMF1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: KCMF1; TNF-a; miR-210; placenta; preeclampsia