miR-101-5p suppresses trophoblast cell migration and invasion via modulating the DUSP6-ERK1/2 axis in preeclampsia

作者全名："Xu, Jiacheng; Wang, Jie; Chen, Miaomiao; Chao, Bingdi; He, Jie; Bai, Yuxiang; Luo, Xiaofang; Liu, Hongli; Xie, Lumei; Tao, Yuelan; Qi, Hongbo; Luo, Xin"

作者地址："[Xu, Jiacheng; Wang, Jie; Chen, Miaomiao; Chao, Bingdi; He, Jie; Bai, Yuxiang; Liu, Hongli; Xie, Lumei; Tao, Yuelan; Qi, Hongbo; Luo, Xin] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Xu, Jiacheng; Wang, Jie; Chao, Bingdi; He, Jie; Liu, Hongli; Xie, Lumei; Tao, Yuelan; Qi, Hongbo; Luo, Xin] Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Chongqing, Peoples R China; [Chen, Miaomiao] Maternal & Child Hlth Hosp Hubei Prov, Wuhan, Hubei, Peoples R China; [Luo, Xiaofang] Chongqing Med Univ, Affiliated Hosp 1, Reprod Med Ctr, Chongqing, Peoples R China; [Qi, Hongbo] Chongqing Med Univ, Women & Childrens Hosp, Chongqing, Peoples R China"

通信作者："Qi, HB; Luo, X (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, 1 Youyi Rd, Chongqing 400016, Peoples R China.; Qi, HB; Luo, X (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Chongqing, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Chongqing, Peoples R China."

来源：JOURNAL OF ASSISTED REPRODUCTION AND GENETICS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001004161600004

JCR分区：Q1

影响因子：3.2

年份：2023

卷号：40

期号：7

开始页：1597

结束页：1610

文献类型：Article

关键词：Preeclampsia; miR-101-5p; DUSP6; ERK1; 2; Migration; Invasion

摘要："PurposeDysregulated behaviors of trophoblast cells leading to defective placentation are considered the main cause of preeclampsia (PE). Abnormal miRNA expression profiles have been observed in PE placental tissue, indicating the significant role of miRNAs in PE development. This study aimed to investigate the expression of miR-101-5p in PE placental tissue and its biological functions.MethodsThe expression of miR-101-5p in placental tissue was detected by quantitative real-time PCR (qRT-PCR). The localization of miR-101-5p in term placental tissue and decidual tissue was determined by the fluorescence in situ hybridization (FISH)-immunofluorescence (IF) double labeling assay. The effect of miR-101-5p on the migration, invasion, proliferation, and apoptosis of the HTR8/SVneo trophoblast cells was investigated. Online databases combined with transcriptomics were used to identify potential target genes and related pathways of miR-101-5p. Finally, the interaction between miR-101-5p and the target gene was verified by qRT-PCT, WB, dual-luciferase reporter assay, and rescue experiments.ResultsThe study found that miR-101-5p was upregulated in PE placental tissue compared to normal controls and was mainly located in various trophoblast cell subtypes in placental and decidual tissues. Overexpression of miR-101-5p impaired the migration and invasion of HTR8/SVneo cells. DUSP6 was identified as a potential downstream target of miR-101-5p. The expression of miR-101-5p was negatively correlated with DUSP6 expression in HTR8/SVneo cells, and miR-101-5p directly bound to the 3 ' UTR region of DUSP6. DUSP6 upregulation rescued the migratory and invasive abilities of HTR8/SVneo cells in the presence of miR-101-5p overexpression. Additionally, miR-101-5p downregulated DUSP6, resulting in enhanced ERK1/2 phosphorylation.ConclusionThis study revealed that miR-101-5p inhibits the migration and invasion of HTR8/SVneo cells by regulating the DUSP6-ERK1/2 axis, providing a new molecular mechanism for the pathogenesis of PE."

基金机构："National Natural Science Foundation of China [82171668, 81771614, 82171662, 81901506, 82001581]; Joint Funds of the National Natural Science Foundation of China [U21A20346]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No. 82171668, No. 81771614, No. 82171662, No. 81901506, No. 82001581) and Joint Funds of the National Natural Science Foundation of China (No. U21A20346)"