PMID- 29885402 OWN - NLM STAT- MEDLINE DCOM- 20190506 LR - 20221207 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 79 DP - 2018 Sep TI - Evaluation of miRNAs expression in medullary thyroid carcinoma tissue samples: miR-34a and miR-144 as promising overexpressed markers in MTC. PG - 212-221 LID - S0046-8177(18)30187-4 [pii] LID - 10.1016/j.humpath.2018.05.019 [doi] AB - 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(-DeltaDeltaCt) 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. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Shabani, Noushin AU - Shabani N AD - Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: n_shabani@ymail.com. FAU - Razaviyan, Javad AU - Razaviyan J AD - Department of Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: javadrazaviyan@gmail.com. FAU - Paryan, Mahdi AU - Paryan M AD - Department of Research and Development, Production and Research Complex, Pasteur Institute of Iran, Tehran. Electronic address: mpayan@gmail.com. FAU - Tavangar, Seyed Mohammad AU - Tavangar SM AD - Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: tavangar@ams.ac.ir. FAU - Azizi, Fereidoun AU - Azizi F AD - Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: aziz@endocrine.ac.ir. FAU - Mohammadi-Yeganeh, Samira AU - Mohammadi-Yeganeh S AD - Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: s.mohammadiyeganeh@sbmu.ac.ir. FAU - Hedayati, Mehdi AU - Hedayati M AD - Cellular and Molecular Endocrine Research Center (CMERC), Research Institute for Endocrine Sciences of Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: hedayati@endocrine.ac.ir. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180606 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (Biomarkers, Tumor) RN - 0 (MIRN144 microRNA, human) RN - 0 (MIRN34 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 0 (Axl Receptor Tyrosine Kinase) RN - 0 (AXL protein, human) RN - Thyroid cancer, medullary SB - IM MH - Adolescent MH - Adult MH - Aged MH - Biomarkers, Tumor/analysis/*genetics MH - Carcinoma, Neuroendocrine/enzymology/*genetics/pathology MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Expression Profiling/methods MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Male MH - MicroRNAs/*genetics MH - Middle Aged MH - Predictive Value of Tests MH - Proto-Oncogene Proteins/analysis/genetics MH - Real-Time Polymerase Chain Reaction MH - Receptor Protein-Tyrosine Kinases/analysis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - TOR Serine-Threonine Kinases/analysis/genetics MH - Thyroid Neoplasms/enzymology/*genetics/pathology MH - Up-Regulation MH - Young Adult MH - Axl Receptor Tyrosine Kinase OTO - NOTNLM OT - AXL OT - MTC OT - mTOR OT - miR-144 OT - miR-34a EDAT- 2018/06/10 06:00 MHDA- 2019/05/07 06:00 CRDT- 2018/06/10 06:00 PHST- 2018/03/10 00:00 [received] PHST- 2018/05/09 00:00 [revised] PHST- 2018/05/24 00:00 [accepted] PHST- 2018/06/10 06:00 [pubmed] PHST- 2019/05/07 06:00 [medline] PHST- 2018/06/10 06:00 [entrez] AID - S0046-8177(18)30187-4 [pii] AID - 10.1016/j.humpath.2018.05.019 [doi] PST - ppublish SO - Hum Pathol. 2018 Sep;79:212-221. doi: 10.1016/j.humpath.2018.05.019. Epub 2018 Jun 6.