Upregulated long noncoding RNA Linc00261 in pre‐eclampsia and its effect on trophoblast invasion and migration via regulating miR‐558/TIMP4 signaling pathway

Abstract

Pre-eclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality but the exact underlying mechanisms of PE pathogenesis remain elusive. Accumulated data suggested that the long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of PE. The present study identified the changes of lncRNA Linc00261 in PE and its effects on trophoblasts invasion and migration. Our results showed that the expression of Linc00261 was upregulated in placental tissues of PE women compared with those of healthy pregnant women. Overexpression of Linc00261 suppressed cell invasion and migration, induced cell apoptosis, and caused cell-cycle arrest at G 0 /G 1 phase of HTR-8/SVneo cells; while knockdown of Linc00261 had the opposite effects on the HTR-8/SVneo cells. Mechanistic studies showed Linc00261 functioned as a competing endogenous RNA for miR-558 in HTR-8/SVneo cells, and miR-558 was negatively regulated by Linc00261. The expression level of miR-558 in the PE group was significantly lower than the control group, and the expression level of Linc00261 was negatively correlated with the expression level of miR-558 in the placental tissues of women with PE. Furthermore, miR-558 was found to negatively regulate the expression of TIMP metallopeptidase inhibitor 4 (TIMP4) via targeting the 3′ untranslated region in the HTR-8/SVneo cells. Overexpression of miR-558 increased HTR-8/SVneo cell invasion and migration, which was attenuated by TIMP4 overexpression. More importantly, both overexpression of miR-558 and knockdown of TIMP4 partially reversed the suppressive effects of Linc00261 overexpression on cell invasion and migration of HTR-8/SVneo cells. Collectively, our results for the first time showed the upregulation of Linc00261 in the placental tissues of severe PE patients. The mechanistic results indicated that Linc00261 exerted the suppressive effects on the trophoblast invasion and migration via targeting miR-558/TIMP4 axis, which may involve in the pathogenesis of PE. K E Y W O R D S invasion and migration, Linc00261, miR-558, pre-eclampsia, TIMP metallopeptidase inhibitor 4, trophoblast J Cell Biochem. 2019;120:13243-13253.wileyonlinelibrary.com/journal/jcb

Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3

“…These studies demonstrate that GATA6 plays a vital role in the progression of disease. Overexpression of LINC00261 suppressed cell proliferation and invasion in human choriocarcinoma [27] and inhibited migration of trophoblast in pre-eclampsia [28].…”

MicroRNA‑524‑5p regulates the proliferation and invasion of HTR‑8/SVneo trophoblasts by targeting NUMB in the Notch signaling pathway

“…In recent years, numerous studies have continued to investigate preeclampsia (1,23), but the exact cause has not yet been elucidated. There is still no ideal animal model that replicates all pathological conditions of preeclampsia that are produced.…”

“…Preeclampsia is a common serious disorder of obstetrics and is a hypertensive complication that occurs after the 20th week of gestation, characterized by new-onset hypertension (1).…”

Empty

“…It is well-documented that LINC00261 exhibited anti-tumor role in different cancers, even though the investigations focused on LINC00261 remain very limited so far. LINC00261-associated ceRNA net has been gradually establishing including LINC00261/miR-132-3p/BCL2L11 in endometriosis [23], LINC00261/miR-558/TIMP4 in pre-eclampsia [24], LINC00261/miR-182, miR-183, miR-153, miR-27a, and miR-96/FOXO1 in endometrial carcinoma [20], and LINC00261/miR-19a/KLF2 in NSCLC ( Figure S3). More and further LINC00261/miRNAs/mRNAs pathways should be revealed in cancers such as lung cancer.…”