Long intergenic noncoding RNA 00473 promoting migration and invasion of trophoblastic cell line HTR‐8/SVneo via regulating miR‐424‐5p‐mediated wnt3a/β‐catenin signaling pathway

Abstract

Background: Preeclampsia (PE) is a serious obstetric complication. Recent studies point out that the functions of long intergenic noncoding RNA 00473 (linc00473), miR-424-5p, and Wnt/β-catenin signaling pathway were involved in the invasion and migration of extravillous trophoblast. Here, we investigated the role and mechanism of linc00473 in HTR-8/SVneo trophoblastic cell line and its role in PE. Method: The expression levels of linc00473 and miR-424-5p in placental tissues and the transfection efficiency of miR-424-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HTR-8/SVneo cell invasion and proliferation were determined by transwell and Cell Counting Kit-8 (CCK-8) assays. The protein expressions of wnt3a, p-GSK3β, GSK3β, active β-catenin, and total β-catenin were detected by Western blot. The apoptosis and migration of HTR-8/SVneo cells were detected by flow cytometry and wound healing assays. The targeting relationships between linc00473, miR-424-5p, and wnt3a were predicted by ENCORI database and TargetScan V7.2 and were determined using dual-luciferase reporter assay.Results: The expression level of linc00473 was low and miR-424-5p was high in placenta of PE patients. Linc00473 can target miR-424-5p, while miR-424-5p target wnt3a. High expression of linc00473 and wnt3a promoted cell proliferation, migration, invasion, and inhibited cell apoptosis. However, miR-424-5p mimic inhibited HTR-8/SVneo cells proliferation, migration, invasion, while promoted cell apoptosis, partially reversed the effect of linc00473, while wnt3a overexpression partially counteracted the effect of miR-424-5p mimic. Conclusion: Linc00473 mediates the regulation of Wnt/β-catenin signaling pathway by miR-424-5p to affect the invasion and migration ability of trophoblastic cell line HTR-8/SVneo. It indicated that linc00473 is involved in PE and could be a therapeutic target.

miR‑424‑5p is downregulated in the placentas of patients with preeclampsia and affects trophoblast migration and invasion

“…Among these targets, miR-424 regulates estrogen-related receptor γ to suppress trophoblast proliferation and invasion ( 50 ). Moreover, miR-424 targeted Wnt3a to influence Wnt/β-catenin signaling pathway and then affected the proliferation, apoptosis, migration and invasion of trophoblast cell line HTR-8/SVneo ( 51 ). In addition to Wnt/catenin signaling pathway, miR-424 also wields its function by regulating other pathways, such as PI3K/AKT signaling pathway in PE ( 40 ).…”

The Role of Non-Coding RNAs in the Human Placenta

“…knockdown in trophoblast cell lines significantly inhibites cell proliferation and promotes apoptosis, whereas overexpression stimulates trophoblast proliferation. Further, linc00473 inhibited the expression of tissue factor pathway inhibitor 2 (TFPI2) through binding to lysinespecific demethylase 1 (LSD1) [177] mediates decidualization of human endometrial stromal cells in response to cAMP signaling [178] downregulation facilitates trophoblast cell migration and invasion via the miR-15a-5p/LITAF axis in pre-eclampsia, [179] Linc00473 mediates regulation of Wnt/β-catenin signaling pathway by miR-424-5p and affects invasion and migration of the trophoblastic cell line HTR-8/SVneo [180] PRNCR1 promotes the progression of PE by modulating the MAPK signaling pathway [181] CCAT1 is highly expressed in PE and can promote the progression of PE by inhibiting the expression of CDK4 [182] MEG3 is lower expressed in the placenta of patients with PE, and its regulation of trophoblast cell epithelial-mesenchymal transition via the TGF-β pathway inhibitor SMAD7 may be the molecular mechanism involved in the pathogenesis of PE [183] TUG1 is modulating proliferation in trophoblast cells via epigenetic suppression of RND3 [184] is modulating proliferation, apoptosis, invasion, and angiogenesis via targeting miR-29b in trophoblast cells [185] is regulating the migration and invasion of trophoblast-like cells through sponging miR-204-5p [186] lnc-DCs overexpression in dendritic cells mediates their maturation by phosphorylating STAT3 and induces the over-maturation of decidual dendritic cells in PE and leads to an increase in Th1 cells [187] RPAIN regulates the invasion and apoptosis of trophoblast cell lines via complement protein C1q [188] ATB down-regulated in PE placentas which was found to decrease migration, proliferation, and tube-formation of HTR-8/SVneo cells [189] Table 3. Cont.…”

The clinical prognostic value of lncRNA LINC00473 in cancer patients: A meta-analysis

“…[ 39 ] Previous study confirmed that the Wnt/β-catenin signaling pathway is of significant importance to the migration and invasion of tumors. [ 40 ] What’s more, Han’s study recommended the downregulation of lncRNA LINC00473 to attenuate the radioresistence of head and neck SCC cells through inhibiting Wnt/β-catenin signaling pathway. [ 40 ] A large body of evidence has demonstrated that LINC00473 might activate hepatocellular carcinoma progression by participating in signaling pathway of phosphatidylinositol-3-kinase/protein kinase B/the mammalian target of Rapamycin, which fortified cell proliferation, migration, invasion, and metastasis.…”

“…[40] What's more, Han's study recommended the downregulation of lncRNA LINC00473 to attenuate the radioresistence of head and neck SCC cells through inhibiting Wnt/β-catenin signaling pathway. [40] A large body of evidence has demonstrated that LINC00473 might activate hepatocellular carcinoma progression by participating in signaling pathway of phosphatidylinositol-3-kinase/ protein kinase B/the mammalian target of Rapamycin, which fortified cell proliferation, migration, invasion, and metastasis. [41] It is known to all that chemoradiotherapy is beneficial for the patients with advanced cancers.…”