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Updated: Jun 14, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
Circ_0076490 silencing inhibits MAPK1 expression to decrease the proliferation and increase apoptosis of Jurkat cells
Qin Ye1, Chengyao Gu2, Wang Yan2
1Department of Pulmonary, Ningbo No.2 Hospital, Ningbo, China.
Background:
Myasthenia gravis (MG) is a both neuromuscular junction and antibody-mediated autoimmune disease, and its pathogenesis involves the regulation of circular RNAs (circRNAs). However, the role of circ_0076490 in MG and the underlying mechanism remain unknown.
Methods:
RNA levels of circ_0076490, microRNA-144-3p (miR-144-3p), and mitogen-activated protein kinase 1 (MAPK1) were detected by quantitative real-time polymerase chain reaction. Cell viability and proliferation were investigated by cell counting kit-8 and 5-Ethynyl-29-deoxyuridine assays, respectively. Cell cycle and apoptosis were assessed by flow cytometry analysis. The putative binding relationship of miR-144-3p and circ_0076490 or MAPK1 was predicted by circular RNA interactome and TargetScan online databases, respectively, and identified through dual-luciferase reporter assay and RNA pull-down assay.
Results:
We observed dramatic increases of circ_0076490 and MAPK1 expression and a decrease of miR-144-3p expression in the peripheral blood of MG patients in comparison with healthy controls. Reduced expression of circ_0076490 induced an inhibitory effect on the proliferation of Jurkat cells and a promoting effect on cell apoptosis. Additionally, miR-144-3p was identified as a target miRNA of circ_0076490, and its depletion attenuated circ_0076490 knockdown-mediated effects on the proliferation and apoptosis of Jurkat cells. MAPK1 was a target gene of miR-144-3p and its overexpression rescued decreased cell proliferation and increased cell apoptosis induced by miR-144-3p introduction. Furthermore, circ_0076490 regulated MAPK1 expression by interacting with miR-144-3p.
Conclusion:
Circ_0076490 knockdown inhibited proliferation and induced apoptosis of Jurkat cells through the regulation of the miR-144-3p/MAPK1 axis, providing potential targets for developing improved therapy of MG.
Insights
Circular RNA circ_0076490 is upregulated in myasthenia gravis (MG) and drives disease progression by inhibiting miR-144-3p, which in turn activates MAPK1. Targeting circ_0076490 offers a potential therapeutic strategy for MG.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction.
- The pathogenesis of MG involves circular RNAs (circRNAs), but the specific role of circ_0076490 remains unclear.
Purpose of the Study:
- To investigate the role of circ_0076490 in myasthenia gravis.
- To elucidate the underlying molecular mechanism involving miR-144-3p and MAPK1.
Main Methods:
- Quantitative real-time PCR to measure RNA levels.
- Cell proliferation, cell cycle, and apoptosis assays (CCK-8, EdU, flow cytometry).
- Bioinformatic prediction and experimental validation (dual-luciferase, RNA pull-down) of RNA interactions.
Main Results:
- Circ_0076490 and MAPK1 expression were elevated, while miR-144-3p was decreased in MG patients.
- Circ_0076490 knockdown inhibited Jurkat cell proliferation and promoted apoptosis.
- Circ_0076490 targets miR-144-3p, which targets MAPK1, forming a regulatory axis.
Conclusions:
- Circ_0076490 knockdown inhibits proliferation and induces apoptosis in Jurkat cells via the miR-144-3p/MAPK1 pathway.
- This circ_0076490/miR-144-3p/MAPK1 axis represents a potential therapeutic target for myasthenia gravis.
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