CircHIPK3 contributes to human villous trophoblast growth, migration and invasion via modulating the pathway of miR-346/KCMF1. (February 2022)

• Record Type: Journal Article
• Authors: Wang, Wenxing; Liu, Jingying; Pan, Enjie
• Is Part Of: Placenta. Volume 118(2022)
• Page Start: 46
• Page End: 54
• Publication Date: 2022-02
• Subjects: circHIPK3 -- miR-346 -- KCMF1 -- Trophoblast -- Preeclampsia; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2021.12.020
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Preeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. The regular growth, migration and invasion of villous trophoblast cells contribute to placental development. The objective of this study was to investigate the role and mechanism of circular RNA homeodomain interacting protein kinase 3 (circHIPK3) in the biological functions of trophoblast cells. Methods: The expression of circHIPK3, microRNA-346 (miR-346) and potassium channel modulatory factor 1 (KCMF1) mRNA was measured by quantitative real-time PCR (qPCR). Trophoblast cell proliferation, migration/invasion and cell cycle progression/apoptosis were determined by CCK-8 assay, transwell assay and flow cytometry assay, respectively. The predicted relationship between miR-346 and circHIPK3 or KCMF1 by bioinformatics was confirmed dual-luciferase reporter assay and RIP assay. Results: CircHIPK3 and KCMF1 were downregulated, while miR-346 was upregulated in placenta tissues from PE patients. The forced expression of circHIPK3 promoted trophoblast cell proliferation and migration/invasion but alleviated cell cycle arrest and cell apoptosis. MiR-346 was a target of circHIPK3, and miR-346 restoration reversed the effects of circHIPK3 upregulation. In addition, circHIPK3 acted as miR-346 sponge to modulate KCMF1 expression. KCMF1 downregulation partially repressed trophoblast cell proliferation, migration and invasion that were facilitated by miR-346 inhibition or circHIPK3 upregulation. Discussion: CircHIPK3 contributes to trophoblast cell proliferation, migration and invasion by upregulating KCMF1 via acting as miR-346 sponge. Highlights: CircHIPK3 is downregulated in placenta tissues from preeclampsia patients. CircHIPK3 overexpression promotes proliferation, migration, invasion and represses apoptosis of villous trophoblast cells. CircHIPK3 acts as miR-346 sponge to inhibit miR-346 expression. MiR-346 targets KCMF1 3′UTR to suppress KCMF1 expression. CircHIPK3 governs the miR-346/KCMF1 pathway to regulate villous trophoblast cell functions.