CircLRRK1 targets miR-223-3p to inhibit the proliferation, migration and invasion of trophoblast cells by regulating the PI3K/AKT signaling pathway. 2021

Rui Tang, and Zhilei Zhang, and Wenjun Han
Department of Obstetrics, Yantaishan Hospital of Yantai, Yantai, 264001, Shandong, China.

Many studies have shown that circular RNAs (circRNAs) are related to the occurrence of preeclampsia (PE). However, the role of circLRRK1 in the progression of PE is unclear. The identification and localization of circLRRK1 were verified by Actinomycin D (ActD) assay, Ribonuclease R (RNase R) digestion assay and subcellular localization assay. Moreover, the proliferation of trophoblast cells was detected by 3-(45)-dimethylthiahiazo (-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and colony formation assay. Furthermore, the migration and invasion of trophoblast cells were determined by wound healing assay and transwell assay. Meanwhile, Western blot (WB) analysis was used to examine the protein levels of migration markers and PI3K/AKT signaling pathway markers. In addition, the interaction between circLRRK1 and miR-223-3p was confirmed by dual-luciferase reporter assay and biotin-labeled RNA pull-down assay. Our results showed that circLRRK1 was significantly highly expressed in PE patients. Silenced circLRRK1 could markedly enhance the proliferation, migration and invasion of trophoblast cells. Additionally, we found that circLRRK1 could target miR-223-3p. MiR-223-3p overexpression also promoted the proliferation, migration and invasion of trophoblast cells. The rescue experiments revealed that miR-223-3p inhibitor could reverse the promoting effect of circLRRK1 silencing on the proliferation, migration and invasion of trophoblast cells. Furthermore, circLRRK1 silencing could activate the PI3K/AKT signaling pathway by targeting miR-223-3p. CircLRRK1 could suppress the proliferation, migration and invasion of trophoblast cells by regulating the PI3K/AKT signaling pathway via targeting miR-223-3p, suggesting that circLRRK1 might be a potential biomarker for the treatment of PE.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000079962 RNA, Circular RNA molecules in which the 3' and 5' ends are covalently joined to form a closed continuous loop. They are resistant to digestion by EXORIBONUCLEASES. Circular Intronic RNA,Circular RNA,Circular RNAs,Closed Circular RNA,ciRNA,circRNA,circRNAs,Circular RNA, Closed,Intronic RNA, Circular,RNA, Circular Intronic,RNA, Closed Circular,RNAs, Circular
D014327 Trophoblasts Cells lining the outside of the BLASTOCYST. After binding to the ENDOMETRIUM, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (PLACENTA). Cytotrophoblasts,Syncytiotrophoblasts,Trophoblast,Cytotrophoblast,Syncytiotrophoblast
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051057 Proto-Oncogene Proteins c-akt Protein-serine-threonine kinases that contain PLECKSTRIN HOMOLOGY DOMAINS and are activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. They play a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells. akt Proto-Oncogene Protein,c-akt Protein,AKT1 Protein Kinase,AKT2 Protein Kinase,AKT3 Protein Kinase,Akt-alpha Protein,Akt-beta Protein,Akt-gamma Protein,Protein Kinase B,Protein Kinase B alpha,Protein Kinase B beta,Protein Kinase B gamma,Protein-Serine-Threonine Kinase (Rac),Proto-Oncogene Protein Akt,Proto-Oncogene Protein RAC,Proto-Oncogene Proteins c-akt1,Proto-Oncogene Proteins c-akt2,Proto-Oncogene Proteins c-akt3,RAC-PK Protein,Rac Protein Kinase,Rac-PK alpha Protein,Rac-PK beta Protein,Related to A and C-Protein,c-akt Proto-Oncogene Protein,Akt alpha Protein,Akt beta Protein,Akt gamma Protein,Akt, Proto-Oncogene Protein,Protein, akt Proto-Oncogene,Protein, c-akt Proto-Oncogene,Proteins c-akt1, Proto-Oncogene,Proteins c-akt2, Proto-Oncogene,Proteins c-akt3, Proto-Oncogene,Proto Oncogene Protein Akt,Proto Oncogene Protein RAC,Proto Oncogene Proteins c akt,Proto Oncogene Proteins c akt1,Proto Oncogene Proteins c akt2,Proto Oncogene Proteins c akt3,Proto-Oncogene Protein, akt,Proto-Oncogene Protein, c-akt,RAC PK Protein,RAC, Proto-Oncogene Protein,Rac PK alpha Protein,Rac PK beta Protein,Related to A and C Protein,akt Proto Oncogene Protein,alpha Protein, Rac-PK,c akt Proto Oncogene Protein,c-akt, Proto-Oncogene Proteins,c-akt1, Proto-Oncogene Proteins,c-akt2, Proto-Oncogene Proteins,c-akt3, Proto-Oncogene Proteins
D019869 Phosphatidylinositol 3-Kinases Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell. PI-3 Kinase,Phosphatidylinositol-3-OH Kinase,PtdIns 3-Kinase,PI 3-Kinase,PI-3K,PI3 Kinases,PI3-Kinase,Phosphoinositide 3 Kinases,Phosphoinositide 3-Hydroxykinase,PtdIns 3-Kinases,3-Hydroxykinase, Phosphoinositide,Kinase, PI-3,Kinase, Phosphatidylinositol-3-OH,Kinases, PI3,Kinases, Phosphoinositide 3,PI 3 Kinase,PI3 Kinase,Phosphatidylinositol 3 Kinases,Phosphatidylinositol 3 OH Kinase,Phosphoinositide 3 Hydroxykinase,PtdIns 3 Kinase,PtdIns 3 Kinases

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