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The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model
[Display omitted] •SNHG16/ miRNA-146a/ TRAF6 signaling pathway induces neoplastic development and metastasis.•ZOL improves the histopathological changes in the colon of mouse model of CRC.•ZOL decreases in expression of CK20 & Ki-67 and increases expression of CDx2 in colon.•ZOL prevents osteopo...
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| Published in: | International immunopharmacology 2024-05, Vol.133, p.112125-112125, Article 112125 |
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| creator | Helmy Mohamed, Amany Noureldin Hassan, Ahmed Hussein Abdel hay, Nesma Fouad Ahmed, Manar El Sawy, Marwa M. Sonbol, Mohamed M. Hussein Mohamed, Reham |
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•SNHG16/ miRNA-146a/ TRAF6 signaling pathway induces neoplastic development and metastasis.•ZOL improves the histopathological changes in the colon of mouse model of CRC.•ZOL decreases in expression of CK20 & Ki-67 and increases expression of CDx2 in colon.•ZOL prevents osteoporotic changes by suppressing RANK-TRAF6 signaling pathway.•ZOL could modify the expression of TRAF6 and its regulators; SNHG16 and miRNA-146a.
Bone fracture as a consequence of colorectal cancer (CRC) and associated osteoporosis (OP) is considered a risk factor for increasing the mortality rate among CRC patients. SNHG16/ miRNA-146a/ TRAF6 signaling pathway is a substantial contributor to neoplastic evolution, progression, and metastasis. Here, we investigated the effect of zoledronate (ZOL) on the growth of CRC and associated OP in a mouse model. Thirty Balb/c mice were divided into Naïve, azoxymethane (AOM)/dextran sodium sulfate (DSS), and ZOL groups. Body weight and small nucleolar RNA host gene 16 (SNHG16) expression, microRNA-146a, and TRAF6 in bone, colon, and stool were investigated. Samples of colon and bone were collected and processed for light microscopic, immunohistochemical staining for cytokeratin 20 (CK20), nuclear protein Ki67 (pKi-67), and caudal type homeobox transcription factor 2 (CDx2) in colon and receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) in bone. A computerized tomography (CT) scan of the femur and tibia was studied. ZOL produced a significant decrease in the expression of SNHG16 and TRAF6 and an increase in miRNA-146a in the colon and bone. ZOL administration improved the histopathological changes in the colon, produced a significant decrease in CK20 and Ki-67, and increased CDx2 expressions. In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6. |
| doi_str_mv | 10.1016/j.intimp.2024.112125 |
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•SNHG16/ miRNA-146a/ TRAF6 signaling pathway induces neoplastic development and metastasis.•ZOL improves the histopathological changes in the colon of mouse model of CRC.•ZOL decreases in expression of CK20 & Ki-67 and increases expression of CDx2 in colon.•ZOL prevents osteoporotic changes by suppressing RANK-TRAF6 signaling pathway.•ZOL could modify the expression of TRAF6 and its regulators; SNHG16 and miRNA-146a.
Bone fracture as a consequence of colorectal cancer (CRC) and associated osteoporosis (OP) is considered a risk factor for increasing the mortality rate among CRC patients. SNHG16/ miRNA-146a/ TRAF6 signaling pathway is a substantial contributor to neoplastic evolution, progression, and metastasis. Here, we investigated the effect of zoledronate (ZOL) on the growth of CRC and associated OP in a mouse model. Thirty Balb/c mice were divided into Naïve, azoxymethane (AOM)/dextran sodium sulfate (DSS), and ZOL groups. Body weight and small nucleolar RNA host gene 16 (SNHG16) expression, microRNA-146a, and TRAF6 in bone, colon, and stool were investigated. Samples of colon and bone were collected and processed for light microscopic, immunohistochemical staining for cytokeratin 20 (CK20), nuclear protein Ki67 (pKi-67), and caudal type homeobox transcription factor 2 (CDx2) in colon and receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) in bone. A computerized tomography (CT) scan of the femur and tibia was studied. ZOL produced a significant decrease in the expression of SNHG16 and TRAF6 and an increase in miRNA-146a in the colon and bone. ZOL administration improved the histopathological changes in the colon, produced a significant decrease in CK20 and Ki-67, and increased CDx2 expressions. In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2024.112125</identifier><identifier>PMID: 38657499</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Azoxymethane - toxicity ; Bone Density Conservation Agents - pharmacology ; Bone Density Conservation Agents - therapeutic use ; Colon - drug effects ; Colon - metabolism ; Colon - pathology ; Colorectal Cancer ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Dextran Sulfate ; Disease Models, Animal ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA-146a ; Osteoporosis ; Osteoporosis - drug therapy ; Osteoporosis - metabolism ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; Signal Transduction - drug effects ; SNHG16 ; TNF Receptor-Associated Factor 6 - genetics ; TNF Receptor-Associated Factor 6 - metabolism ; TRAF6 ; Zoledronate ; Zoledronic Acid - therapeutic use</subject><ispartof>International immunopharmacology, 2024-05, Vol.133, p.112125-112125, Article 112125</ispartof><rights>2024 Elsevier B.V.</rights><rights>Copyright © 2024 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c311t-ee2d41a5e29f16592fe0f041b31a2b999a60f39ddc1391142f4fa29dc8ed60143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38657499$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Helmy Mohamed, Amany</creatorcontrib><creatorcontrib>Noureldin Hassan, Ahmed</creatorcontrib><creatorcontrib>Hussein Abdel hay, Nesma</creatorcontrib><creatorcontrib>Fouad Ahmed, Manar</creatorcontrib><creatorcontrib>El Sawy, Marwa M.</creatorcontrib><creatorcontrib>Sonbol, Mohamed M.</creatorcontrib><creatorcontrib>Hussein Mohamed, Reham</creatorcontrib><title>The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>[Display omitted]
•SNHG16/ miRNA-146a/ TRAF6 signaling pathway induces neoplastic development and metastasis.•ZOL improves the histopathological changes in the colon of mouse model of CRC.•ZOL decreases in expression of CK20 & Ki-67 and increases expression of CDx2 in colon.•ZOL prevents osteoporotic changes by suppressing RANK-TRAF6 signaling pathway.•ZOL could modify the expression of TRAF6 and its regulators; SNHG16 and miRNA-146a.
Bone fracture as a consequence of colorectal cancer (CRC) and associated osteoporosis (OP) is considered a risk factor for increasing the mortality rate among CRC patients. SNHG16/ miRNA-146a/ TRAF6 signaling pathway is a substantial contributor to neoplastic evolution, progression, and metastasis. Here, we investigated the effect of zoledronate (ZOL) on the growth of CRC and associated OP in a mouse model. Thirty Balb/c mice were divided into Naïve, azoxymethane (AOM)/dextran sodium sulfate (DSS), and ZOL groups. Body weight and small nucleolar RNA host gene 16 (SNHG16) expression, microRNA-146a, and TRAF6 in bone, colon, and stool were investigated. Samples of colon and bone were collected and processed for light microscopic, immunohistochemical staining for cytokeratin 20 (CK20), nuclear protein Ki67 (pKi-67), and caudal type homeobox transcription factor 2 (CDx2) in colon and receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) in bone. A computerized tomography (CT) scan of the femur and tibia was studied. ZOL produced a significant decrease in the expression of SNHG16 and TRAF6 and an increase in miRNA-146a in the colon and bone. ZOL administration improved the histopathological changes in the colon, produced a significant decrease in CK20 and Ki-67, and increased CDx2 expressions. In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6.</description><subject>Animals</subject><subject>Azoxymethane - toxicity</subject><subject>Bone Density Conservation Agents - pharmacology</subject><subject>Bone Density Conservation Agents - therapeutic use</subject><subject>Colon - drug effects</subject><subject>Colon - metabolism</subject><subject>Colon - pathology</subject><subject>Colorectal Cancer</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Dextran Sulfate</subject><subject>Disease Models, Animal</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA-146a</subject><subject>Osteoporosis</subject><subject>Osteoporosis - drug therapy</subject><subject>Osteoporosis - metabolism</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>SNHG16</subject><subject>TNF Receptor-Associated Factor 6 - genetics</subject><subject>TNF Receptor-Associated Factor 6 - metabolism</subject><subject>TRAF6</subject><subject>Zoledronate</subject><subject>Zoledronic Acid - therapeutic use</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9UU1v1DAQjRCIlsI_QMhHLtl6HMdZX5BWFf2QqiKV5Wx57fHWqyQOcbao_Ch-IxOl5Ygs2aPxm_dm5hXFR-Ar4KDOD6vYT7EbVoILuQIQIOpXxSmsm3UJDa9fU1yrpqwbpU-KdzkfOKe8hLfFSbVWdSO1Pi3-bB-QDWlC4rItG1OLLAX2_e76ijRYF-_vNiVIZc_Z9n5zqViO-962sd-zwU4Pv-wTiz2bZpKRWNwUH5FhCBTNPL-Jz4-ptxMyu7exzxNzqU0j_ZOcs73DkdneM5tzcpFwnqU8YRrSmHLMM3uXjhnp9ti-L94E22b88PyeFT8uv24vrsvbb1c3F5vb0lUAU4kovARbo9ABVK1FQB5o9F0FVuy01lbxUGnvHVQaQIoggxXauzV6xUFWZ8XnhZem-nnEPJkuZodta3ukbkzFpapB0SGoXKCOGs4jBjOMsbPjkwFuZqfMwSxOmdkpszhFZZ-eFY67Dv2_ohdrCPBlASDN-RhxNNlFpH35OG_P-BT_r_AXIFeoMQ</recordid><startdate>20240530</startdate><enddate>20240530</enddate><creator>Helmy Mohamed, Amany</creator><creator>Noureldin Hassan, Ahmed</creator><creator>Hussein Abdel hay, Nesma</creator><creator>Fouad Ahmed, Manar</creator><creator>El Sawy, Marwa M.</creator><creator>Sonbol, Mohamed M.</creator><creator>Hussein Mohamed, Reham</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20240530</creationdate><title>The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model</title><author>Helmy Mohamed, Amany ; Noureldin Hassan, Ahmed ; Hussein Abdel hay, Nesma ; Fouad Ahmed, Manar ; El Sawy, Marwa M. ; Sonbol, Mohamed M. ; Hussein Mohamed, Reham</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c311t-ee2d41a5e29f16592fe0f041b31a2b999a60f39ddc1391142f4fa29dc8ed60143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Azoxymethane - toxicity</topic><topic>Bone Density Conservation Agents - pharmacology</topic><topic>Bone Density Conservation Agents - therapeutic use</topic><topic>Colon - drug effects</topic><topic>Colon - metabolism</topic><topic>Colon - pathology</topic><topic>Colorectal Cancer</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Dextran Sulfate</topic><topic>Disease Models, Animal</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA-146a</topic><topic>Osteoporosis</topic><topic>Osteoporosis - drug therapy</topic><topic>Osteoporosis - metabolism</topic><topic>RNA, Long Noncoding - genetics</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>SNHG16</topic><topic>TNF Receptor-Associated Factor 6 - genetics</topic><topic>TNF Receptor-Associated Factor 6 - metabolism</topic><topic>TRAF6</topic><topic>Zoledronate</topic><topic>Zoledronic Acid - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Helmy Mohamed, Amany</creatorcontrib><creatorcontrib>Noureldin Hassan, Ahmed</creatorcontrib><creatorcontrib>Hussein Abdel hay, Nesma</creatorcontrib><creatorcontrib>Fouad Ahmed, Manar</creatorcontrib><creatorcontrib>El Sawy, Marwa M.</creatorcontrib><creatorcontrib>Sonbol, Mohamed M.</creatorcontrib><creatorcontrib>Hussein Mohamed, Reham</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Helmy Mohamed, Amany</au><au>Noureldin Hassan, Ahmed</au><au>Hussein Abdel hay, Nesma</au><au>Fouad Ahmed, Manar</au><au>El Sawy, Marwa M.</au><au>Sonbol, Mohamed M.</au><au>Hussein Mohamed, Reham</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2024-05-30</date><risdate>2024</risdate><volume>133</volume><spage>112125</spage><epage>112125</epage><pages>112125-112125</pages><artnum>112125</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>[Display omitted]
•SNHG16/ miRNA-146a/ TRAF6 signaling pathway induces neoplastic development and metastasis.•ZOL improves the histopathological changes in the colon of mouse model of CRC.•ZOL decreases in expression of CK20 & Ki-67 and increases expression of CDx2 in colon.•ZOL prevents osteoporotic changes by suppressing RANK-TRAF6 signaling pathway.•ZOL could modify the expression of TRAF6 and its regulators; SNHG16 and miRNA-146a.
Bone fracture as a consequence of colorectal cancer (CRC) and associated osteoporosis (OP) is considered a risk factor for increasing the mortality rate among CRC patients. SNHG16/ miRNA-146a/ TRAF6 signaling pathway is a substantial contributor to neoplastic evolution, progression, and metastasis. Here, we investigated the effect of zoledronate (ZOL) on the growth of CRC and associated OP in a mouse model. Thirty Balb/c mice were divided into Naïve, azoxymethane (AOM)/dextran sodium sulfate (DSS), and ZOL groups. Body weight and small nucleolar RNA host gene 16 (SNHG16) expression, microRNA-146a, and TRAF6 in bone, colon, and stool were investigated. Samples of colon and bone were collected and processed for light microscopic, immunohistochemical staining for cytokeratin 20 (CK20), nuclear protein Ki67 (pKi-67), and caudal type homeobox transcription factor 2 (CDx2) in colon and receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) in bone. A computerized tomography (CT) scan of the femur and tibia was studied. ZOL produced a significant decrease in the expression of SNHG16 and TRAF6 and an increase in miRNA-146a in the colon and bone. ZOL administration improved the histopathological changes in the colon, produced a significant decrease in CK20 and Ki-67, and increased CDx2 expressions. In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>38657499</pmid><doi>10.1016/j.intimp.2024.112125</doi><tpages>1</tpages></addata></record> |
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| source | ScienceDirect Journals |
| subjects | Animals Azoxymethane - toxicity Bone Density Conservation Agents - pharmacology Bone Density Conservation Agents - therapeutic use Colon - drug effects Colon - metabolism Colon - pathology Colorectal Cancer Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Dextran Sulfate Disease Models, Animal Humans Male Mice Mice, Inbred BALB C MicroRNAs - genetics MicroRNAs - metabolism miRNA-146a Osteoporosis Osteoporosis - drug therapy Osteoporosis - metabolism RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism Signal Transduction - drug effects SNHG16 TNF Receptor-Associated Factor 6 - genetics TNF Receptor-Associated Factor 6 - metabolism TRAF6 Zoledronate Zoledronic Acid - therapeutic use |
| title | The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model |
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