miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain · Alnoor Digital Repository

Title: miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain
Abstract: Aims: Pain is a profoundly debilitating symptom in cancer patients, leading to disability, immobility, and a marked decline in their quality of life. This study aimed to investigate the potential roles of miR-199a-3p in a murine model of bone cancer pain induced by tumor cell implantation in the medullary cavity of the femur.

Materials and methods: We assessed pain-related behaviors, including the paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF). To investigate miRNA expression and its targets in astrocytes, we employed a combination of RNA-seq analysis, qRT-PCR, Western blotting, EdU, TUNEL, ChIP, ELISA, and luciferase reporter assays in mice (C3H/HeJ) with bone cancer pain and control groups.

Key findings: On days 10, 14, 21, and 28 post-surgery, we observed significant differences in PWTL, PWMT, and NSF when compared to the sham group (P < 0.001). qRT-PCR assays and miRNA sequencing results confirmed reduced miR-199a-3p expression in astrocytes of mice with bone cancer pain. Gain- and loss-of-function experiments demonstrated that miR-199a-3p suppressed astrocyte activation and the expression of inflammatory cytokines. In vitro investigations revealed that miR-199a-3p mimics reduced the levels of inflammatory factors in astrocytes and MyD88/NF-κB proteins. Furthermore, treatment with a miR-199a-3p agonist resulted in reduced expression of MyD88, TAK1, p-p65, and inflammatory mediators, along with decreased astrocyte activation in the spinal cord.

Significance: Collectively, these findings demonstrate that upregulation of miR-199a-3p may offer a therapeutic avenue for mitigating bone cancer pain in mice by suppressing neuroinflammation and inhibiting the MyD88/NF-κB signaling pathway.
Scientific Type: غير معروف
Link: https://www.sciencedirect.com/science/article/abs/pii/S0024320523007749
Journal volume: vol.333,No.122139
Collaboration type: مشترك
Publish Date: November 15, 2023
Participated Universities (Publication): Alnoor University
Scopus status: In Scopus
Scopus index year: 2 023
Scopus quarter: 1
Scopus citation score: 11.5
Clarivate status: In Clarivate
Clarivate index year: 2 023
Clarivate impafact: 6.78000021
Pub. Med. status: In PubMed
Author (Publication): ضحى غسان يونس حميد
Journal (Publication): Life Sciences
Publisher (Publication): Elsevier
ISSN: 0024-3205
Country (Publication): United kingdom
Country type: عالمية
College (Publication): College of Pharmacy
Departement (Publication): Department of Pharmacy