Evaluation of miRNAs expression in medullary thyroid carcinoma tissue samples: miR-34a and miR-144 as promising overexpressed markers in MTC
Medullary thyroid carcinoma (MTC) is a rare neoplasia derived from neural parafollicular C cells. MicroRNAs (miRNAs) are small regulatory RNAs with essential roles in the biology of cancers such as MTC and can be applied as diagnostic markers. According to previous studies, miR-144 and miR-34 and th...
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description | Medullary thyroid carcinoma (MTC) is a rare neoplasia derived from neural parafollicular C cells. MicroRNAs (miRNAs) are small regulatory RNAs with essential roles in the biology of cancers such as MTC and can be applied as diagnostic markers. According to previous studies, miR-144 and miR-34 and their two oncogenes target, mammalian target of rapamycin (mTOR) and AXL receptor tyrosine kinase (AXL), were selected for further investigations in our study. Thirty MTC samples as well as thirty adjacent normal thyroid tissues were applied in this study including 28 formalin-fixed, paraffin-embedded (FFPE) and 2 fresh-frozen MTC samples. RNA extraction and complementary DNA (cDNA) synthesis were performed for all samples. After primer pairs and probes were designed, real-time polymerase chain reaction (real-time PCR) method was used, and the results were analyzed using 2−ΔΔCt method. Receiver operating characteristic (ROC) curve analysis was applied to assess the diagnostic value of the two miRNAs. AXL protein level was measured in all clinical samples using enzyme-linked immunosorbent assay (ELISA) method. Both miRNAs were up-regulated in all clinical samples compared to the normal tissues. AXL was up-regulated in most clinical samples while mTOR was down-regulated in most samples. Furthermore, the level of AXL protein increased. ROC curve analysis demonstrated that increased expression of miR-34a and miR-144 in MTC patients had significant predictive value. The results demonstrated that high expression of miR-144 and miR-34a can be considered as biomarkers of MTC. However, there was no statistically significant correlation between the expression of these miRNAs and target genes in MTC clinical samples.
•Abnormal expression of miRNAs has been reported in different cancers including medullary thyroid carcinoma (MTC).•miR-144 and miR-34 as well as their candidate target genes including mTOR and AXL were selected in our study.•AXL was up-regulated in most clinical samples while mTOR was down-regulated in most samples.•Both miRNAs were up-regulated in all clinical samples compared to the normal tissues.•High expression of miR-144 and miR-34a can be considered as biomarkers of MTC. |
doi_str_mv | 10.1016/j.humpath.2018.05.019 |
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•Abnormal expression of miRNAs has been reported in different cancers including medullary thyroid carcinoma (MTC).•miR-144 and miR-34 as well as their candidate target genes including mTOR and AXL were selected in our study.•AXL was up-regulated in most clinical samples while mTOR was down-regulated in most samples.•Both miRNAs were up-regulated in all clinical samples compared to the normal tissues.•High expression of miR-144 and miR-34a can be considered as biomarkers of MTC.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2018.05.019</identifier><identifier>PMID: 29885402</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>AXL ; Enzymes ; Gene expression ; Kinases ; Lymphatic system ; Medical prognosis ; Metastasis ; miR-144 ; miR-34a ; Mortality ; MTC ; mTOR ; Proteins ; Studies ; Thyroid cancer</subject><ispartof>Human pathology, 2018-09, Vol.79, p.212-221</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Sep 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-519f4fb8fb2d7ce1b9bf68b2cfe7142cee03ffb4cbdfb9480cce4c1bc62f8be33</citedby><cites>FETCH-LOGICAL-c393t-519f4fb8fb2d7ce1b9bf68b2cfe7142cee03ffb4cbdfb9480cce4c1bc62f8be33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.humpath.2018.05.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29885402$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shabani, Noushin</creatorcontrib><creatorcontrib>Razaviyan, Javad</creatorcontrib><creatorcontrib>Paryan, Mahdi</creatorcontrib><creatorcontrib>Tavangar, Seyed Mohammad</creatorcontrib><creatorcontrib>Azizi, Fereidoun</creatorcontrib><creatorcontrib>Mohammadi-Yeganeh, Samira</creatorcontrib><creatorcontrib>Hedayati, Mehdi</creatorcontrib><title>Evaluation of miRNAs expression in medullary thyroid carcinoma tissue samples: miR-34a and miR-144 as promising overexpressed markers in MTC</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Medullary thyroid carcinoma (MTC) is a rare neoplasia derived from neural parafollicular C cells. MicroRNAs (miRNAs) are small regulatory RNAs with essential roles in the biology of cancers such as MTC and can be applied as diagnostic markers. According to previous studies, miR-144 and miR-34 and their two oncogenes target, mammalian target of rapamycin (mTOR) and AXL receptor tyrosine kinase (AXL), were selected for further investigations in our study. Thirty MTC samples as well as thirty adjacent normal thyroid tissues were applied in this study including 28 formalin-fixed, paraffin-embedded (FFPE) and 2 fresh-frozen MTC samples. RNA extraction and complementary DNA (cDNA) synthesis were performed for all samples. After primer pairs and probes were designed, real-time polymerase chain reaction (real-time PCR) method was used, and the results were analyzed using 2−ΔΔCt method. Receiver operating characteristic (ROC) curve analysis was applied to assess the diagnostic value of the two miRNAs. AXL protein level was measured in all clinical samples using enzyme-linked immunosorbent assay (ELISA) method. Both miRNAs were up-regulated in all clinical samples compared to the normal tissues. AXL was up-regulated in most clinical samples while mTOR was down-regulated in most samples. Furthermore, the level of AXL protein increased. ROC curve analysis demonstrated that increased expression of miR-34a and miR-144 in MTC patients had significant predictive value. The results demonstrated that high expression of miR-144 and miR-34a can be considered as biomarkers of MTC. However, there was no statistically significant correlation between the expression of these miRNAs and target genes in MTC clinical samples.
•Abnormal expression of miRNAs has been reported in different cancers including medullary thyroid carcinoma (MTC).•miR-144 and miR-34 as well as their candidate target genes including mTOR and AXL were selected in our study.•AXL was up-regulated in most clinical samples while mTOR was down-regulated in most samples.•Both miRNAs were up-regulated in all clinical samples compared to the normal tissues.•High expression of miR-144 and miR-34a can be considered as biomarkers of MTC.</description><subject>AXL</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Kinases</subject><subject>Lymphatic system</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>miR-144</subject><subject>miR-34a</subject><subject>Mortality</subject><subject>MTC</subject><subject>mTOR</subject><subject>Proteins</subject><subject>Studies</subject><subject>Thyroid cancer</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFkcFu1DAQhi0EotvCI4AsceGSYDv2xuGCqlUplUqRUDlbtjNmvSRxsJMV-w48dB12y4ELJ4-sb_75Z36EXlFSUkLX73bldu5HPW1LRqgsiSgJbZ6gFRUVK2TVsKdoRQhfF5LW9Rk6T2lHCKWCi-fojDVSCk7YCv2-2utu1pMPAw4O9_7r3WXC8GuMkNLy6QfcQzt3nY4HPG0PMfgWWx2tH0Kv8eRTmgEn3Y8dpPeLQFFxjfXQ_qkp51gnPMbQ--SH7zjsIZ7kISM6_oCYlimf7zcv0DOnuwQvT-8F-vbx6n7zqbj9cn2zubwtbNVUUyFo47gz0hnW1haoaYxbS8Osg5pyZgFI5Zzh1rTONFwSa4FbauyaOWmgqi7Q26NutvVzhjSpbM5C3nGAMCfFiGCS1ITLjL75B92FOQ7ZnWJU1JJU-fyZEkfKxpBSBKfG6PNuB0WJWuJSO3WKSy1xKSJUjiv3vT6pzyZf-W_XYz4Z-HAEIJ9j7yGqZD0MFlofwU6qDf4_Ix4A8K-roQ</recordid><startdate>201809</startdate><enddate>201809</enddate><creator>Shabani, Noushin</creator><creator>Razaviyan, Javad</creator><creator>Paryan, Mahdi</creator><creator>Tavangar, Seyed Mohammad</creator><creator>Azizi, Fereidoun</creator><creator>Mohammadi-Yeganeh, Samira</creator><creator>Hedayati, Mehdi</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201809</creationdate><title>Evaluation of miRNAs expression in medullary thyroid carcinoma tissue samples: miR-34a and miR-144 as promising overexpressed markers in MTC</title><author>Shabani, Noushin ; Razaviyan, Javad ; Paryan, Mahdi ; Tavangar, Seyed Mohammad ; Azizi, Fereidoun ; Mohammadi-Yeganeh, Samira ; Hedayati, Mehdi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-519f4fb8fb2d7ce1b9bf68b2cfe7142cee03ffb4cbdfb9480cce4c1bc62f8be33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>AXL</topic><topic>Enzymes</topic><topic>Gene expression</topic><topic>Kinases</topic><topic>Lymphatic system</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>miR-144</topic><topic>miR-34a</topic><topic>Mortality</topic><topic>MTC</topic><topic>mTOR</topic><topic>Proteins</topic><topic>Studies</topic><topic>Thyroid cancer</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shabani, Noushin</creatorcontrib><creatorcontrib>Razaviyan, Javad</creatorcontrib><creatorcontrib>Paryan, Mahdi</creatorcontrib><creatorcontrib>Tavangar, Seyed Mohammad</creatorcontrib><creatorcontrib>Azizi, Fereidoun</creatorcontrib><creatorcontrib>Mohammadi-Yeganeh, Samira</creatorcontrib><creatorcontrib>Hedayati, Mehdi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shabani, Noushin</au><au>Razaviyan, Javad</au><au>Paryan, Mahdi</au><au>Tavangar, Seyed Mohammad</au><au>Azizi, Fereidoun</au><au>Mohammadi-Yeganeh, Samira</au><au>Hedayati, Mehdi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of miRNAs expression in medullary thyroid carcinoma tissue samples: miR-34a and miR-144 as promising overexpressed markers in MTC</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2018-09</date><risdate>2018</risdate><volume>79</volume><spage>212</spage><epage>221</epage><pages>212-221</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Medullary thyroid carcinoma (MTC) is a rare neoplasia derived from neural parafollicular C cells. MicroRNAs (miRNAs) are small regulatory RNAs with essential roles in the biology of cancers such as MTC and can be applied as diagnostic markers. According to previous studies, miR-144 and miR-34 and their two oncogenes target, mammalian target of rapamycin (mTOR) and AXL receptor tyrosine kinase (AXL), were selected for further investigations in our study. Thirty MTC samples as well as thirty adjacent normal thyroid tissues were applied in this study including 28 formalin-fixed, paraffin-embedded (FFPE) and 2 fresh-frozen MTC samples. RNA extraction and complementary DNA (cDNA) synthesis were performed for all samples. After primer pairs and probes were designed, real-time polymerase chain reaction (real-time PCR) method was used, and the results were analyzed using 2−ΔΔCt method. Receiver operating characteristic (ROC) curve analysis was applied to assess the diagnostic value of the two miRNAs. AXL protein level was measured in all clinical samples using enzyme-linked immunosorbent assay (ELISA) method. Both miRNAs were up-regulated in all clinical samples compared to the normal tissues. AXL was up-regulated in most clinical samples while mTOR was down-regulated in most samples. Furthermore, the level of AXL protein increased. ROC curve analysis demonstrated that increased expression of miR-34a and miR-144 in MTC patients had significant predictive value. The results demonstrated that high expression of miR-144 and miR-34a can be considered as biomarkers of MTC. However, there was no statistically significant correlation between the expression of these miRNAs and target genes in MTC clinical samples.
•Abnormal expression of miRNAs has been reported in different cancers including medullary thyroid carcinoma (MTC).•miR-144 and miR-34 as well as their candidate target genes including mTOR and AXL were selected in our study.•AXL was up-regulated in most clinical samples while mTOR was down-regulated in most samples.•Both miRNAs were up-regulated in all clinical samples compared to the normal tissues.•High expression of miR-144 and miR-34a can be considered as biomarkers of MTC.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29885402</pmid><doi>10.1016/j.humpath.2018.05.019</doi><tpages>10</tpages></addata></record> |
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subjects | AXL Enzymes Gene expression Kinases Lymphatic system Medical prognosis Metastasis miR-144 miR-34a Mortality MTC mTOR Proteins Studies Thyroid cancer |
title | Evaluation of miRNAs expression in medullary thyroid carcinoma tissue samples: miR-34a and miR-144 as promising overexpressed markers in MTC |
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