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miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain
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...
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| Published in: | Life sciences (1973) 2023-11, Vol.333, p.122139-122139, Article 122139 |
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| container_title | Life sciences (1973) |
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| creator | Saadh, Mohamed J. Rashed, Amera Bekhatroh Jamal, Azfar Castillo-Acobo, Roxana Yolanda Kamal, Mohammad Azhar Cotrina-Aliaga, Juan Carlos Gonzáles, José Luis Arias Alothaim, Abdulaziz S. Alhoqail, Wardah A. Ahmad, Fuzail Lakshmaiya, Natrayan Amin, Ali H. Younus, Dhuha Ghassan Rojas, Gregorio Gilmer Rosales Bahrami, Abolfazl Akhavan-Sigari, Reza |
| description | 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.
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.
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 |
| doi_str_mv | 10.1016/j.lfs.2023.122139 |
| format | article |
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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.
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.
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.
•miR-199a-3p alleviates bone cancer pain by suppressing neuroinflammation.•Novel insights into the therapeutic potential of miR-199a-3p in bone cancer pain.•Inhibition of the MyD88/NF-κB pathway by miR-199a-3p attenuates astrocyte activation.•miR-199a-3p reduces inflammatory cytokines, offering a promising pain management strategy.•miRNAs hold promise as a therapeutic target for improving the quality of life in cancer patients.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2023.122139</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>agonists ; animal models ; Astrocyte activation ; astrocytes ; Bone cancer pain ; cytokines ; femur ; loss-of-function mutation ; luciferase ; mice ; microRNA ; miR-199a-3p ; MyD88 ; neoplasm cells ; Neuroinflammation ; NF-κB signaling pathway ; pain ; quality of life ; sequence analysis ; spinal cord ; therapeutics</subject><ispartof>Life sciences (1973), 2023-11, Vol.333, p.122139-122139, Article 122139</ispartof><rights>2023 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c315t-f7b7cdfb9b6e6390d645bc84d72097c096b8051f9b3e2a491a95cb75b77490083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Saadh, Mohamed J.</creatorcontrib><creatorcontrib>Rashed, Amera Bekhatroh</creatorcontrib><creatorcontrib>Jamal, Azfar</creatorcontrib><creatorcontrib>Castillo-Acobo, Roxana Yolanda</creatorcontrib><creatorcontrib>Kamal, Mohammad Azhar</creatorcontrib><creatorcontrib>Cotrina-Aliaga, Juan Carlos</creatorcontrib><creatorcontrib>Gonzáles, José Luis Arias</creatorcontrib><creatorcontrib>Alothaim, Abdulaziz S.</creatorcontrib><creatorcontrib>Alhoqail, Wardah A.</creatorcontrib><creatorcontrib>Ahmad, Fuzail</creatorcontrib><creatorcontrib>Lakshmaiya, Natrayan</creatorcontrib><creatorcontrib>Amin, Ali H.</creatorcontrib><creatorcontrib>Younus, Dhuha Ghassan</creatorcontrib><creatorcontrib>Rojas, Gregorio Gilmer Rosales</creatorcontrib><creatorcontrib>Bahrami, Abolfazl</creatorcontrib><creatorcontrib>Akhavan-Sigari, Reza</creatorcontrib><title>miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain</title><title>Life sciences (1973)</title><description>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.
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.
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.
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.
•miR-199a-3p alleviates bone cancer pain by suppressing neuroinflammation.•Novel insights into the therapeutic potential of miR-199a-3p in bone cancer pain.•Inhibition of the MyD88/NF-κB pathway by miR-199a-3p attenuates astrocyte activation.•miR-199a-3p reduces inflammatory cytokines, offering a promising pain management strategy.•miRNAs hold promise as a therapeutic target for improving the quality of life in cancer patients.</description><subject>agonists</subject><subject>animal models</subject><subject>Astrocyte activation</subject><subject>astrocytes</subject><subject>Bone cancer pain</subject><subject>cytokines</subject><subject>femur</subject><subject>loss-of-function mutation</subject><subject>luciferase</subject><subject>mice</subject><subject>microRNA</subject><subject>miR-199a-3p</subject><subject>MyD88</subject><subject>neoplasm cells</subject><subject>Neuroinflammation</subject><subject>NF-κB signaling pathway</subject><subject>pain</subject><subject>quality of life</subject><subject>sequence analysis</subject><subject>spinal cord</subject><subject>therapeutics</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNqFkUFr3DAQhUVJoJtNf0BvOubi7UiyLIueStq0gQ2BkJyFJI8XLbbsSN7C_vtqcc_tZeby3sy8-Qj5zGDHgDVfjruhzzsOXOwY50zoD2TDWqUraAS7IhsAXleCg_xIbnI-AoCUSmxIGMNLxbS2lZhpPs1zwpwx04inNIXYD3Yc7RKmSN2ZdiGhX4YzXWw64BLigT6dv7ctDZFaOk6njKV2ONCpp26KSL2NHhOdbYi35Lq3Q8ZPf_uWvD38eL3_Ve2ffz7ef9tXXjC5VL1yyne9067BRmjomlo639ad4qCVB924FiTrtRPIba2Z1dI7JZ1StQZoxZbcrXPnNL2fMC9mDNnjMNiI5UJTtogSmJf4_5PyVnGmtGx0kbJV6tOUc8LezCmMNp0NA3MhYI6mEDAXAmYlUDxfVw-WuL8DJpN9wPKQ9Y-mm8I_3H8A7E-NKg</recordid><startdate>20231115</startdate><enddate>20231115</enddate><creator>Saadh, Mohamed J.</creator><creator>Rashed, Amera Bekhatroh</creator><creator>Jamal, Azfar</creator><creator>Castillo-Acobo, Roxana Yolanda</creator><creator>Kamal, Mohammad Azhar</creator><creator>Cotrina-Aliaga, Juan Carlos</creator><creator>Gonzáles, José Luis Arias</creator><creator>Alothaim, Abdulaziz S.</creator><creator>Alhoqail, Wardah A.</creator><creator>Ahmad, Fuzail</creator><creator>Lakshmaiya, Natrayan</creator><creator>Amin, Ali H.</creator><creator>Younus, Dhuha Ghassan</creator><creator>Rojas, Gregorio Gilmer Rosales</creator><creator>Bahrami, Abolfazl</creator><creator>Akhavan-Sigari, Reza</creator><general>Elsevier Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20231115</creationdate><title>miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain</title><author>Saadh, Mohamed J. ; Rashed, Amera Bekhatroh ; Jamal, Azfar ; Castillo-Acobo, Roxana Yolanda ; Kamal, Mohammad Azhar ; Cotrina-Aliaga, Juan Carlos ; Gonzáles, José Luis Arias ; Alothaim, Abdulaziz S. ; Alhoqail, Wardah A. ; Ahmad, Fuzail ; Lakshmaiya, Natrayan ; Amin, Ali H. ; Younus, Dhuha Ghassan ; Rojas, Gregorio Gilmer Rosales ; Bahrami, Abolfazl ; Akhavan-Sigari, Reza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c315t-f7b7cdfb9b6e6390d645bc84d72097c096b8051f9b3e2a491a95cb75b77490083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>agonists</topic><topic>animal models</topic><topic>Astrocyte activation</topic><topic>astrocytes</topic><topic>Bone cancer pain</topic><topic>cytokines</topic><topic>femur</topic><topic>loss-of-function mutation</topic><topic>luciferase</topic><topic>mice</topic><topic>microRNA</topic><topic>miR-199a-3p</topic><topic>MyD88</topic><topic>neoplasm cells</topic><topic>Neuroinflammation</topic><topic>NF-κB signaling pathway</topic><topic>pain</topic><topic>quality of life</topic><topic>sequence analysis</topic><topic>spinal cord</topic><topic>therapeutics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saadh, Mohamed J.</creatorcontrib><creatorcontrib>Rashed, Amera Bekhatroh</creatorcontrib><creatorcontrib>Jamal, Azfar</creatorcontrib><creatorcontrib>Castillo-Acobo, Roxana Yolanda</creatorcontrib><creatorcontrib>Kamal, Mohammad Azhar</creatorcontrib><creatorcontrib>Cotrina-Aliaga, Juan Carlos</creatorcontrib><creatorcontrib>Gonzáles, José Luis Arias</creatorcontrib><creatorcontrib>Alothaim, Abdulaziz S.</creatorcontrib><creatorcontrib>Alhoqail, Wardah A.</creatorcontrib><creatorcontrib>Ahmad, Fuzail</creatorcontrib><creatorcontrib>Lakshmaiya, Natrayan</creatorcontrib><creatorcontrib>Amin, Ali H.</creatorcontrib><creatorcontrib>Younus, Dhuha Ghassan</creatorcontrib><creatorcontrib>Rojas, Gregorio Gilmer Rosales</creatorcontrib><creatorcontrib>Bahrami, Abolfazl</creatorcontrib><creatorcontrib>Akhavan-Sigari, Reza</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saadh, Mohamed J.</au><au>Rashed, Amera Bekhatroh</au><au>Jamal, Azfar</au><au>Castillo-Acobo, Roxana Yolanda</au><au>Kamal, Mohammad Azhar</au><au>Cotrina-Aliaga, Juan Carlos</au><au>Gonzáles, José Luis Arias</au><au>Alothaim, Abdulaziz S.</au><au>Alhoqail, Wardah A.</au><au>Ahmad, Fuzail</au><au>Lakshmaiya, Natrayan</au><au>Amin, Ali H.</au><au>Younus, Dhuha Ghassan</au><au>Rojas, Gregorio Gilmer Rosales</au><au>Bahrami, Abolfazl</au><au>Akhavan-Sigari, Reza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain</atitle><jtitle>Life sciences (1973)</jtitle><date>2023-11-15</date><risdate>2023</risdate><volume>333</volume><spage>122139</spage><epage>122139</epage><pages>122139-122139</pages><artnum>122139</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>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.
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.
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.
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.
•miR-199a-3p alleviates bone cancer pain by suppressing neuroinflammation.•Novel insights into the therapeutic potential of miR-199a-3p in bone cancer pain.•Inhibition of the MyD88/NF-κB pathway by miR-199a-3p attenuates astrocyte activation.•miR-199a-3p reduces inflammatory cytokines, offering a promising pain management strategy.•miRNAs hold promise as a therapeutic target for improving the quality of life in cancer patients.</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.lfs.2023.122139</doi><tpages>1</tpages></addata></record> |
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| subjects | agonists animal models Astrocyte activation astrocytes Bone cancer pain cytokines femur loss-of-function mutation luciferase mice microRNA miR-199a-3p MyD88 neoplasm cells Neuroinflammation NF-κB signaling pathway pain quality of life sequence analysis spinal cord therapeutics |
| title | miR-199a-3p suppresses neuroinflammation by directly targeting MyD88 in a mouse model of bone cancer pain |
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