Circulating myomiRNAs as biomarkers in patients with Cushing’s syndrome
Purpose Impairment of skeletal muscle mass and strength affects 40–70% of patients with active Cushing’s syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbati...
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| Veröffentlicht in: | Journal of endocrinological investigation 2024-03, Vol.47 (3), p.655-669 |
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| creator | Pivonello, C. Patalano, R. Simeoli, C. Montò, T. Negri, M. Amatrudo, F. Di Paola, N. Larocca, A. Crescenzo, E. M. Pirchio, R. Solari, D. de Angelis, C. Auriemma, R. S. Cavallo, L. M. Colao, A. Pivonello, R. |
| description | Purpose
Impairment of skeletal muscle mass and strength affects 40–70% of patients with active Cushing’s syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbation. The aim of the current study is to explore changes in circulating myomiRs in CS patients compared to healthy controls and their involvement in IGFI/PI3K/Akt/mTOR pathway regulation in skeletal muscle.
Methods
C2C12, mouse myocytes, were exposed to hydrocortisone (HC), and atrophy-related gene expression was investigated by RT-qPCR, WB and IF to assess HC-mediated atrophic signalling. miRNAs were evaluated in HC-treated C2C12 by PCR Arrays. MyomiRs significantly overexpressed in C2C12 were investigated in 37 CS patients and 24 healthy controls serum by RT-qPCR. The anti-anabolic role of circulating miRNAs significantly upregulated in CS patients was explored in C2C12 by investigating the IGFI/PI3K/Akt/mTOR pathway regulation.
Results
HC induced higher expression of atrophy-related genes, miR-133a-3p, miR-122-5p and miR-200b-3p in C2C12 compared to untreated cells. Conversely, the anabolic IGFI/PI3K/Akt/mTOR signalling was reduced and this effect was mediated by miR-133a-3p. In CS patients miR-133a-3p and miR-200b-3p revealed higher circulating levels (
p
|
| doi_str_mv | 10.1007/s40618-023-02184-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2863302965</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2933508930</sourcerecordid><originalsourceid>FETCH-LOGICAL-c370t-ca5494dffad861b4fb100cae738cd263f1f5eead4793d3ff38eee899a6bd6fae3</originalsourceid><addsrcrecordid>eNp9kMtOwzAQRS0EolD4ARYoEhs2ASeTOs6yinhUqkBCsLacZNym5FE8iVB3_Aa_x5dgaHmIBYuRR_K5d2YuY0cBPws4j88p4iKQPg_BVSAjH7bYXhCH3JcgxfavfsD2iRacQwwy3mUDiIUMowT22CQtbd5XuiubmVev2rq8uxmTp8nLyrbW9hEteWXjLR2BTUfec9nNvbSnuRO8vbySR6umsG2NB2zH6IrwcPMO2cPlxX167U9vrybpeOrnEPPOz_UoSqLCGF1IEWSRydwtuUa3WV6EAkxgRoi6iOIECjAGJCLKJNEiK4TRCEN2uvZd2vapR-pUXVKOVaUbbHtSoRQAPEzEyKEnf9BF29vGbafCBGDEZQLcUeGaym1LZNGopS3d6SsVcPURtFoHrVzQ6jNoBU50vLHusxqLb8lXsg6ANUDuq5mh_Zn9j-07ASCKpA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2933508930</pqid></control><display><type>article</type><title>Circulating myomiRNAs as biomarkers in patients with Cushing’s syndrome</title><source>SpringerLink Journals</source><creator>Pivonello, C. ; Patalano, R. ; Simeoli, C. ; Montò, T. ; Negri, M. ; Amatrudo, F. ; Di Paola, N. ; Larocca, A. ; Crescenzo, E. M. ; Pirchio, R. ; Solari, D. ; de Angelis, C. ; Auriemma, R. S. ; Cavallo, L. M. ; Colao, A. ; Pivonello, R.</creator><creatorcontrib>Pivonello, C. ; Patalano, R. ; Simeoli, C. ; Montò, T. ; Negri, M. ; Amatrudo, F. ; Di Paola, N. ; Larocca, A. ; Crescenzo, E. M. ; Pirchio, R. ; Solari, D. ; de Angelis, C. ; Auriemma, R. S. ; Cavallo, L. M. ; Colao, A. ; Pivonello, R.</creatorcontrib><description>Purpose
Impairment of skeletal muscle mass and strength affects 40–70% of patients with active Cushing’s syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbation. The aim of the current study is to explore changes in circulating myomiRs in CS patients compared to healthy controls and their involvement in IGFI/PI3K/Akt/mTOR pathway regulation in skeletal muscle.
Methods
C2C12, mouse myocytes, were exposed to hydrocortisone (HC), and atrophy-related gene expression was investigated by RT-qPCR, WB and IF to assess HC-mediated atrophic signalling. miRNAs were evaluated in HC-treated C2C12 by PCR Arrays. MyomiRs significantly overexpressed in C2C12 were investigated in 37 CS patients and 24 healthy controls serum by RT-qPCR. The anti-anabolic role of circulating miRNAs significantly upregulated in CS patients was explored in C2C12 by investigating the IGFI/PI3K/Akt/mTOR pathway regulation.
Results
HC induced higher expression of atrophy-related genes, miR-133a-3p, miR-122-5p and miR-200b-3p in C2C12 compared to untreated cells. Conversely, the anabolic IGFI/PI3K/Akt/mTOR signalling was reduced and this effect was mediated by miR-133a-3p. In CS patients miR-133a-3p and miR-200b-3p revealed higher circulating levels (
p
< 0.0001, respectively) compared to controls. ROC curves for miR-133a-3p (AUC 0.823,
p
< 0.0001) and miR-200b-3p (AUC 0.850,
p
< 0.0001) demonstrated that both myomiRs represent potential biomarkers to discriminate between CS and healthy subjects. Pearson’s correlation analysis revealed that circulating levels of miR-133a-3p are directly correlated with 24 h urinary-free cortisol level (
r
= 0.468,
p
= 0.004) in CS patients.
Conclusions
HC induces atrophic signals by miR-133a-3p overexpression in mouse myocytes and humans. Circulating miR-133a-3p is promising biomarkers of hypercortisolism.</description><identifier>ISSN: 1720-8386</identifier><identifier>ISSN: 0391-4097</identifier><identifier>EISSN: 1720-8386</identifier><identifier>DOI: 10.1007/s40618-023-02184-3</identifier><identifier>PMID: 37682493</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adrenocorticotropic hormone ; AKT protein ; Atrophy ; Biomarkers ; Chromosome 3 ; Chromosome 5 ; Correlation analysis ; Endocrinology ; Gene expression ; Hydrocortisone ; Insulin-like growth factor I ; Internal Medicine ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; MicroRNAs ; miRNA ; Musculoskeletal system ; Myocytes ; Nervous system diseases ; Original Article ; Pituitary ; Signal transduction ; Skeletal muscle ; TOR protein</subject><ispartof>Journal of endocrinological investigation, 2024-03, Vol.47 (3), p.655-669</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c370t-ca5494dffad861b4fb100cae738cd263f1f5eead4793d3ff38eee899a6bd6fae3</cites><orcidid>0000-0002-9632-1348</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40618-023-02184-3$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40618-023-02184-3$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37682493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pivonello, C.</creatorcontrib><creatorcontrib>Patalano, R.</creatorcontrib><creatorcontrib>Simeoli, C.</creatorcontrib><creatorcontrib>Montò, T.</creatorcontrib><creatorcontrib>Negri, M.</creatorcontrib><creatorcontrib>Amatrudo, F.</creatorcontrib><creatorcontrib>Di Paola, N.</creatorcontrib><creatorcontrib>Larocca, A.</creatorcontrib><creatorcontrib>Crescenzo, E. M.</creatorcontrib><creatorcontrib>Pirchio, R.</creatorcontrib><creatorcontrib>Solari, D.</creatorcontrib><creatorcontrib>de Angelis, C.</creatorcontrib><creatorcontrib>Auriemma, R. S.</creatorcontrib><creatorcontrib>Cavallo, L. M.</creatorcontrib><creatorcontrib>Colao, A.</creatorcontrib><creatorcontrib>Pivonello, R.</creatorcontrib><title>Circulating myomiRNAs as biomarkers in patients with Cushing’s syndrome</title><title>Journal of endocrinological investigation</title><addtitle>J Endocrinol Invest</addtitle><addtitle>J Endocrinol Invest</addtitle><description>Purpose
Impairment of skeletal muscle mass and strength affects 40–70% of patients with active Cushing’s syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbation. The aim of the current study is to explore changes in circulating myomiRs in CS patients compared to healthy controls and their involvement in IGFI/PI3K/Akt/mTOR pathway regulation in skeletal muscle.
Methods
C2C12, mouse myocytes, were exposed to hydrocortisone (HC), and atrophy-related gene expression was investigated by RT-qPCR, WB and IF to assess HC-mediated atrophic signalling. miRNAs were evaluated in HC-treated C2C12 by PCR Arrays. MyomiRs significantly overexpressed in C2C12 were investigated in 37 CS patients and 24 healthy controls serum by RT-qPCR. The anti-anabolic role of circulating miRNAs significantly upregulated in CS patients was explored in C2C12 by investigating the IGFI/PI3K/Akt/mTOR pathway regulation.
Results
HC induced higher expression of atrophy-related genes, miR-133a-3p, miR-122-5p and miR-200b-3p in C2C12 compared to untreated cells. Conversely, the anabolic IGFI/PI3K/Akt/mTOR signalling was reduced and this effect was mediated by miR-133a-3p. In CS patients miR-133a-3p and miR-200b-3p revealed higher circulating levels (
p
< 0.0001, respectively) compared to controls. ROC curves for miR-133a-3p (AUC 0.823,
p
< 0.0001) and miR-200b-3p (AUC 0.850,
p
< 0.0001) demonstrated that both myomiRs represent potential biomarkers to discriminate between CS and healthy subjects. Pearson’s correlation analysis revealed that circulating levels of miR-133a-3p are directly correlated with 24 h urinary-free cortisol level (
r
= 0.468,
p
= 0.004) in CS patients.
Conclusions
HC induces atrophic signals by miR-133a-3p overexpression in mouse myocytes and humans. Circulating miR-133a-3p is promising biomarkers of hypercortisolism.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adrenocorticotropic hormone</subject><subject>AKT protein</subject><subject>Atrophy</subject><subject>Biomarkers</subject><subject>Chromosome 3</subject><subject>Chromosome 5</subject><subject>Correlation analysis</subject><subject>Endocrinology</subject><subject>Gene expression</subject><subject>Hydrocortisone</subject><subject>Insulin-like growth factor I</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Musculoskeletal system</subject><subject>Myocytes</subject><subject>Nervous system diseases</subject><subject>Original Article</subject><subject>Pituitary</subject><subject>Signal transduction</subject><subject>Skeletal muscle</subject><subject>TOR protein</subject><issn>1720-8386</issn><issn>0391-4097</issn><issn>1720-8386</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp9kMtOwzAQRS0EolD4ARYoEhs2ASeTOs6yinhUqkBCsLacZNym5FE8iVB3_Aa_x5dgaHmIBYuRR_K5d2YuY0cBPws4j88p4iKQPg_BVSAjH7bYXhCH3JcgxfavfsD2iRacQwwy3mUDiIUMowT22CQtbd5XuiubmVev2rq8uxmTp8nLyrbW9hEteWXjLR2BTUfec9nNvbSnuRO8vbySR6umsG2NB2zH6IrwcPMO2cPlxX167U9vrybpeOrnEPPOz_UoSqLCGF1IEWSRydwtuUa3WV6EAkxgRoi6iOIECjAGJCLKJNEiK4TRCEN2uvZd2vapR-pUXVKOVaUbbHtSoRQAPEzEyKEnf9BF29vGbafCBGDEZQLcUeGaym1LZNGopS3d6SsVcPURtFoHrVzQ6jNoBU50vLHusxqLb8lXsg6ANUDuq5mh_Zn9j-07ASCKpA</recordid><startdate>20240301</startdate><enddate>20240301</enddate><creator>Pivonello, C.</creator><creator>Patalano, R.</creator><creator>Simeoli, C.</creator><creator>Montò, T.</creator><creator>Negri, M.</creator><creator>Amatrudo, F.</creator><creator>Di Paola, N.</creator><creator>Larocca, A.</creator><creator>Crescenzo, E. M.</creator><creator>Pirchio, R.</creator><creator>Solari, D.</creator><creator>de Angelis, C.</creator><creator>Auriemma, R. S.</creator><creator>Cavallo, L. M.</creator><creator>Colao, A.</creator><creator>Pivonello, R.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9632-1348</orcidid></search><sort><creationdate>20240301</creationdate><title>Circulating myomiRNAs as biomarkers in patients with Cushing’s syndrome</title><author>Pivonello, C. ; Patalano, R. ; Simeoli, C. ; Montò, T. ; Negri, M. ; Amatrudo, F. ; Di Paola, N. ; Larocca, A. ; Crescenzo, E. M. ; Pirchio, R. ; Solari, D. ; de Angelis, C. ; Auriemma, R. S. ; Cavallo, L. M. ; Colao, A. ; Pivonello, R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-ca5494dffad861b4fb100cae738cd263f1f5eead4793d3ff38eee899a6bd6fae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Adrenocorticotropic hormone</topic><topic>AKT protein</topic><topic>Atrophy</topic><topic>Biomarkers</topic><topic>Chromosome 3</topic><topic>Chromosome 5</topic><topic>Correlation analysis</topic><topic>Endocrinology</topic><topic>Gene expression</topic><topic>Hydrocortisone</topic><topic>Insulin-like growth factor I</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>MicroRNAs</topic><topic>miRNA</topic><topic>Musculoskeletal system</topic><topic>Myocytes</topic><topic>Nervous system diseases</topic><topic>Original Article</topic><topic>Pituitary</topic><topic>Signal transduction</topic><topic>Skeletal muscle</topic><topic>TOR protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pivonello, C.</creatorcontrib><creatorcontrib>Patalano, R.</creatorcontrib><creatorcontrib>Simeoli, C.</creatorcontrib><creatorcontrib>Montò, T.</creatorcontrib><creatorcontrib>Negri, M.</creatorcontrib><creatorcontrib>Amatrudo, F.</creatorcontrib><creatorcontrib>Di Paola, N.</creatorcontrib><creatorcontrib>Larocca, A.</creatorcontrib><creatorcontrib>Crescenzo, E. M.</creatorcontrib><creatorcontrib>Pirchio, R.</creatorcontrib><creatorcontrib>Solari, D.</creatorcontrib><creatorcontrib>de Angelis, C.</creatorcontrib><creatorcontrib>Auriemma, R. S.</creatorcontrib><creatorcontrib>Cavallo, L. M.</creatorcontrib><creatorcontrib>Colao, A.</creatorcontrib><creatorcontrib>Pivonello, R.</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of endocrinological investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pivonello, C.</au><au>Patalano, R.</au><au>Simeoli, C.</au><au>Montò, T.</au><au>Negri, M.</au><au>Amatrudo, F.</au><au>Di Paola, N.</au><au>Larocca, A.</au><au>Crescenzo, E. M.</au><au>Pirchio, R.</au><au>Solari, D.</au><au>de Angelis, C.</au><au>Auriemma, R. S.</au><au>Cavallo, L. M.</au><au>Colao, A.</au><au>Pivonello, R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating myomiRNAs as biomarkers in patients with Cushing’s syndrome</atitle><jtitle>Journal of endocrinological investigation</jtitle><stitle>J Endocrinol Invest</stitle><addtitle>J Endocrinol Invest</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>47</volume><issue>3</issue><spage>655</spage><epage>669</epage><pages>655-669</pages><issn>1720-8386</issn><issn>0391-4097</issn><eissn>1720-8386</eissn><abstract>Purpose
Impairment of skeletal muscle mass and strength affects 40–70% of patients with active Cushing’s syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbation. The aim of the current study is to explore changes in circulating myomiRs in CS patients compared to healthy controls and their involvement in IGFI/PI3K/Akt/mTOR pathway regulation in skeletal muscle.
Methods
C2C12, mouse myocytes, were exposed to hydrocortisone (HC), and atrophy-related gene expression was investigated by RT-qPCR, WB and IF to assess HC-mediated atrophic signalling. miRNAs were evaluated in HC-treated C2C12 by PCR Arrays. MyomiRs significantly overexpressed in C2C12 were investigated in 37 CS patients and 24 healthy controls serum by RT-qPCR. The anti-anabolic role of circulating miRNAs significantly upregulated in CS patients was explored in C2C12 by investigating the IGFI/PI3K/Akt/mTOR pathway regulation.
Results
HC induced higher expression of atrophy-related genes, miR-133a-3p, miR-122-5p and miR-200b-3p in C2C12 compared to untreated cells. Conversely, the anabolic IGFI/PI3K/Akt/mTOR signalling was reduced and this effect was mediated by miR-133a-3p. In CS patients miR-133a-3p and miR-200b-3p revealed higher circulating levels (
p
< 0.0001, respectively) compared to controls. ROC curves for miR-133a-3p (AUC 0.823,
p
< 0.0001) and miR-200b-3p (AUC 0.850,
p
< 0.0001) demonstrated that both myomiRs represent potential biomarkers to discriminate between CS and healthy subjects. Pearson’s correlation analysis revealed that circulating levels of miR-133a-3p are directly correlated with 24 h urinary-free cortisol level (
r
= 0.468,
p
= 0.004) in CS patients.
Conclusions
HC induces atrophic signals by miR-133a-3p overexpression in mouse myocytes and humans. Circulating miR-133a-3p is promising biomarkers of hypercortisolism.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>37682493</pmid><doi>10.1007/s40618-023-02184-3</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-9632-1348</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1720-8386 |
| ispartof | Journal of endocrinological investigation, 2024-03, Vol.47 (3), p.655-669 |
| issn | 1720-8386 0391-4097 1720-8386 |
| language | eng |
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| source | SpringerLink Journals |
| subjects | 1-Phosphatidylinositol 3-kinase Adrenocorticotropic hormone AKT protein Atrophy Biomarkers Chromosome 3 Chromosome 5 Correlation analysis Endocrinology Gene expression Hydrocortisone Insulin-like growth factor I Internal Medicine Medicine Medicine & Public Health Metabolic Diseases MicroRNAs miRNA Musculoskeletal system Myocytes Nervous system diseases Original Article Pituitary Signal transduction Skeletal muscle TOR protein |
| title | Circulating myomiRNAs as biomarkers in patients with Cushing’s syndrome |
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