Razi Journal of Medical Sciences

fa بررسی ارتباط میکرو RNA های منتخب با مهاجم بودن پاتولوژی تومور در بیماران سرطان پاپیلری تیروئید Investigation of Some Selected micro RNAs Association with Aggressiveness of Tumor Pathology in Cases of Papillary Thyroid Carcinoma ژنتیک Genetic پژوهشي Research <div style="text-align: justify;">زمینه و هدف: شایعترین بدخیمی غده تیروئید، سرطان پاپیلاری تیروئید (Papillary Thyroid Carcinoma-PTC) میباشد و به نظر میرسد که میکرو RNA (mir) های دخیل در PTC، بر تهاجم تومورها اثر میگذارند. در این مطالعه به بررسی بیان mir-16-5p، mir-34b-5p، mir-146b-5p، mir-877-5p و Let-7f-5p در نمونهی سرم و بافت توموری تیروئید بیماران PTC پرداخته شده است. روش کار: در این مطالعهی مورد-شاهدی، تعداد 36 بیمار دارای PTC شامل 18 مورد تهاجمی و 18 مورد غیر تهاجمی وارد مطالعه شدند. بررسی بیان ژن با استفاده از روش real-time PCR انجام شده و مقادیر چند برابری تغییرات (FC) گزارش گردید. یافته ها: به طور خلاصه، mir-16 افزایش بیان معنادار در خون (2.85= FC، 0.024= P)، mir-34 کاهش بیان معنادار هم در خون (0.19= FC، 0.001> P) و هم در بافت تومور (0.19= FC، 0.001> P)، mir-146 افزایش بیان معنادار هم در خون (48.10= FC، 0.001> P) و هم در بافت تومور (60.61= FC، 0.001> P)، mir-877 کاهش بیان معنادار در خون (0.22= FC، 0.001> P)، و Let-7 کاهش بیان معنادار هم در خون (0.09= FC، 0.001> P) و هم در بافت تومور (0.13= FC، 0.001> P) را نشان دادند. نتیجه گیری: میکرو RNA های منتخب مورد بررسی ارتباط معناداری با تهاجمی بودن تومورهای PTC دارد. با استفاده از مطالعات بیوانفورماتیک میتوان سعی در تبیین مکانیسمهای مرتبط نمود. </div> <div style="text-align: justify;">Background & Aims: Papillary thyroid carcinoma (PTC) is the most prevalent thyroid gland tumor arising from thyroid follicular cells. MicroRNAs (miRs) are endogenous single‑stranded non‑coding RNAs attaching to the different sites of the target mRNAs, leading to regulation of gene expression. Hence, miRs play a role in biological functions. Diagnostic role of miRs in PTC has been previously studied. However, the results of such molecular studies should be reinvestigated among different ancestries worldwide. Despite the fact, other than diagnosis, it is vital to have capability to discriminate aggressive cases from the non-aggressive ones to prevent over-diagnosis and over-treatment. Hence, the current investigation was performed to study the association of let-7f, miR-146b-5p, miR-34b, miR-16 and miR-877-5p expression in blood serum and tumor tissue with aggressiveness of PTC in an Iranian population. Methods: This was a case control study. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to compare blood and tumor tissue expression of the miRs between aggressive and non-aggressive PTC samples. Eighteen patients with aggressive PTC were considered as the case group and 18 patients with non-aggressive PTC as the control group. Samples were taken from three hospitals as Toos, Shariyati and Firoozgar (Tehran, Iran). A written informed consent was obtained from each participant. Fresh tissue specimens of aggressive and non-aggressive PTC tissues were obtained from tumors and instantly kept at -80 °C until assessment. Two independent pathologists assessed the samples. PTC was confirmed by light microscope using hematoxylin and eosin staining. Total RNA was extracted with columnar extraction method using total RNA purification kit (Norgen, Canada) according to the manufacturer's instructions. Sample quality control was using cel-mir-39 Spike-In Kit (Norgen, Canada) which offers a quantified synthetic RNA (cel-miR-39) for spike-in. Cel-mir-39 was used for normalization in RT-qPCR assay as the reference to state ∆Ct. cDNA was synthesized with poly A polymerase technique using microScript microRNA cDNA Synthesis kit (Norgen, Canada). Afterwards, the cDNA was used for real-time reverse transcriptase polymerase chain reaction (RT-PCR) using SYBR Green mastermix (Norgen, Canada). Fold changes (FC) of each miR were computed via the formula 2-∆∆CT in Excel 2013 calibrating with the mean of expression in non-aggressive PTC patients. Significance of individual FCs was assessed with one sample t test (FC = 1 was the null hypothesis). Besides, FC between blood serum and tumor tissue was performed through independent t test at the significance level of 0.05. Results: MiR-16 had a meaningful surge in blood (FC = 2.85; P = 0.024), while miR-34 showed a meaningful down-regulation in blood (FC = 0.19; P < 0.001) and tumor tissue (FC = 0.19; P < 0.001). In addition, miR-146 had a major up-regulation in blood (FC = 48.10; P < 0.001) and tumor tissue (FC = 60.61; P < 0.001), miR-877 a momentous down-regulation in blood (FC = 0.22; P < 0.001), and let-7 a meaningful down-regulation in blood (FC = 0.09; P < 0.001) and tumor tissue (FC = 0.13; P < 0.001). Independent t test was used to compare FC of each miR (blood expression versus tumor tissue expression). MiR-16 exhibited a meaningful up-regulation in aggressive PTC samples (2.85 vs 0.92; P = 0.020). However, no major difference was reported between blood and tumor tissue FCs for other miRs. Conclusion: MiRs can help to differentiate invasive PTC from non-invasive PTC. Concisely, miR-16 and miR-877 had an upregulation in blood, miR-34 and let-7 a down regulation in blood and tumor tissue, miR-146 an upregulation in blood and tumor tissue, and miR-146 a significant up regulation in blood and tumor tissue. Expression alteration of miR-16 was meaningfully more prevailing in blood compared with tumor tissue in favor of upregulation. Among the studied miRs, miR-146 was the most frequently occurring result in this study and previous studies. Predictive role of these biomarkers should be assessed in further well-designed cohort investigations, then the results can be utilized as personalized medicine in the management of PTC. </div> سرطان پاپیلاری تیروئید, میکرو RNA, ژن‌های سرکوب کننده تومور, پروتوانکوژن Papillary thyroid Carcinoma, microRNA, tumor Suppressor genes, Proto-oncogenes 1 9 http://rjms.iums.ac.ir/browse.php?a_code=A-10-6915-1&slc_lang=fa&sid=1 Sara Nazari سارا نظری 3900319475328460090763 3900319475328460090763 No Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran گروه زیست شناسی سلولی مولکولی، دانشکده علوم زیستی دانشگاه آزاد اسلامی واحد تهران شمال، تهران، ایران Ahmad Majd احمد مجد 3900319475328460090764 3900319475328460090764 No Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran گروه زیست شناسی سلولی مولکولی، دانشکده علوم زیستی دانشگاه آزاد اسلامی واحد تهران شمال، تهران، ایران Iraj Heydari ایرج حیدری 3900319475328460090765 3900319475328460090765 No Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran مرکز تحقیقات غدد درون ریز و متابولیسم، پژوهشکده غدد درون ریز و متابولیسم، دانشگاه علوم پزشکی ایران، تهران، ایران Mohammad Reza Mohajeri Tehrani محمدرضا مهاجری طهرانی 3900319475328460090766 3900319475328460090766 No Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran مرکز تحقیقات غدد درون ریز و متابولیسم، پژوهشکده علوم غدد و متابولیسم بالینی، دانشگاه علوم پزشکی تهران، تهران، ایران Reza Nekouian رضا نکوئیان nekouian.r@iums.ac.ir 3900319475328460090767 3900319475328460090767 Yes Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran مرکز تحقیقات رشد و تکامل کودکان، پژوهشکده غدد و متابولیسم، دانشگاه علوم پزشکی ایران، تهران، ایران