Journal Article

Hsa_circ_0004872 alleviates meningioma progression by sponging miR-190a-3p/PTEN signaling

Yuan, Wen, Liu, Anmin, Wu, Zhihui, Peng, Junmin, Huang, Yongkai, Peng, Zewei, Han, Deqing

2024

Overview

Background Meningioma, the most prevalent intracranial tumor, possesses a significant propensity for malignant transformation. Circular RNAs (circ-RNAs), a class of non-coding RNAs, have emerged as crucial players in tumorigenesis. This study explores the functional relevance of hsa_circ_0004872, a specific circ-RNA, in the context of meningioma. Methods Molecular structure and stability of hsa_circ_0004872 were elucidated through PCR identification. Meningioma cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. Gene and protein expression were analyzed via qRT-PCR and western blot. Molecular interactions were confirmed through dual-luciferase reporter gene and RIP assays. Results Hsa_circ_0004872, derived from exons 2 to 4 of the host gene MAPK1, demonstrated enhanced stability compared to its host MAPK1. Clinical data described that hsa_circ_0004872 was reduced in meningioma tissues and cell lines, and negatively correlated to poor survival rate of meningioma patients. Overexpression of hsa_circ_0004872 exhibited inhibitory effects on cell proliferation and promotion of apoptosis in vitro. Subsequent investigations unveiled a direct interaction between hsa_circ_0004872 and miR-190a-3p, leading to the activation of the PI3K/AKT signaling pathway through targeting PTEN. Notably, miR-190a-3p silence accelerated the apoptosis and proliferation inhibition of meningioma cells by inactivating PTEN/PI3K/AKT signaling, while miR-190a-3p overexpression showed an opposite effect, which greatly reversed the anti-tumor effects of hsa_circ_0004872 overexpression. Conclusion In summary, our findings highlighted the intricate role of hsa_circ_0004872 in meningioma, shedding light on the regulatory mechanisms involving circ-RNAs in tumor progression. This positions hsa_circ_0004872 as a potential key regulatory factor in meningioma with implications for future therapeutic interventions. Highlights Hsa_circ_0004872 exhibits low expression in meningioma, correlating with a diminished survival rate among patients. Overexpression of hsa_circ_0004872 impedes meningioma cell proliferation while enhancing apoptosis. Hsa_circ_0004872 acts as a negative regulator of miR-190a-3p by functioning as a miRNA sponge. Upregulation of miR-190a-3p counteracts the anti-tumor effects induced by hsa_circ_0004872 overexpression in vitro. Inhibition of miR-190a-3p reduces cell proliferation and heightens apoptosis by targeting the PTEN/PI3K/AKT signaling pathway.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 1-Phosphatidylinositol 3-kinase / AKT protein / Analysis / Antibodies / Apoptosis / Biomedical and Life Sciences / Biomedicine / Brain cancer / Cancer Research / Care and treatment / Cell growth / Cell proliferation / Cervical cancer / Cholecystokinin / Circular RNA / Development and progression / Exons / Flow cytometry / Gastric cancer / Gene expression / Gene flow / Genetic aspects / Glioma / Health aspects / Health Promotion and Disease Prevention / hsa_circ_0004872 / Kinases / Laboratory animals / Medicine/Public Health / Meningioma / MicroRNAs / miR-190a-3p / Oncology / Plasmids / Polymerase chain reaction / PTEN protein / PTEN/PI3K/AKT pathway / Reporter gene / Signal transduction / Statistical analysis / Surgical Oncology / Therapeutic applications / Tumorigenesis / Tumors