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

被引：4

作者：

Saadh, Mohamed J. ^{[1
]}

Rashed, Amera Bekhatroh ^{[2
]}

Jamal, Azfar ^{[3
,4
]}

Castillo-Acobo, Roxana Yolanda ^{[5
]}

Kamal, Mohammad Azhar ^{[6
]}

Cotrina-Aliaga, Juan Carlos ^{[7
]}

Gonzales, Jose Luis Arias ^{[8
]}

Alothaim, Abdulaziz S. ^{[4
]}

Alhoqail, Wardah A. ^{[9
]}

Ahmad, Fuzail ^{[10
]}

Lakshmaiya, Natrayan ^{[11
]}

Amin, Ali H. ^{[12
]}

Younus, Dhuha Ghassan ^{[13
]}

Rojas, Gregorio Gilmer Rosales ^{[14
]}

Bahrami, Abolfazl ^{[15
]}

Akhavan-Sigari, Reza ^{[16
,17
]}

机构：

[1] Middle East Univ, Fac Pharm, Amman 11831, Jordan

[2] Jouf Univ, Coll Appl Med Sci, Nursing Dept, Sakaka, Saudi Arabia

[3] Majmaah Univ, Hlth & Basic Sci Res Ctr, Majmaah 11952, Saudi Arabia

[4] Majmaah Univ, Coll Sci, Dept Biol, Al Zulfi 11952, Saudi Arabia

[5] Univ Nacl San Agustin Arequipa, Arequipa, Peru

[6] Prince Sattam Bin Abdulaziz Univ, Coll Pharm, Dept Pharmaceut, Alkharj 11942, Saudi Arabia

[7] Univ Peruana Los Andes, Fac Ingn, Huancayo, Peru

[8] Univ British Columbia, Fac Social Studies, Dept Social Sci, Vancouver, BC, Canada

[9] Majmaah Univ, Coll Sci, Dept Biol, Al Majmaah 11952, Saudi Arabia

[10] AlMaarefa Univ, Coll Appl Sci, Riyadh 13713, Saudi Arabia

[11] Saveetha Sch Engn SIMATS, Dept Mech Engn, Chennai, Tamil Nadu, India

[12] Mansoura Univ, Fac Sci, Zool Dept, Mansoura 35516, Egypt

[13] Al Noor Univ Coll, Dept Pharm, Nineveh, Iraq

[14] Univ Peruana Los Andes, Huancayo, Peru

[15] Ludwig Maximilians Univ Munchen, Biomed Ctr Syst Biol Sci Munich, Munich, Germany

[16] Univ Med Ctr Tuebingen, Dept Neurosurg, Tubingen, Germany

[17] Coll Humanum Warsaw Management Univ, Dept Hlth Care Management & Clin Res, Warsaw, Poland

来源：

LIFE SCIENCES | 2023年 / 333卷

关键词：

miR-199a-3p; MyD88; NF-kappa B signaling pathway; Neuroinflammation; Astrocyte activation; Bone cancer pain; NF-KAPPA-B; RAT MODEL; NEUROPATHIC PAIN; MURINE MODEL; SPINAL-CORD; MESENCHYMAL TRANSITION; NEUROCHEMICAL CHANGES; ZOLEDRONIC ACID; DOWN-REGULATION; METASTASIS;

D O I：

10.1016/j.lfs.2023.122139

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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-kappa B 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-kappa B signaling pathway.

引用

页数：14

共 81 条

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