Jigari-Asl, Farinaz, Khordadmehr, Monireh, baradaran, Behzad, Baghbani, Elham, Noorolyai, Saeed, Rahmani, Shima, Saberivand, Adel. (1403). Restoration of miR-451a-5p/miR-34a-5p could suppress the proliferation and migration of human breast cancer cells through Wnt/β- catenin and ERK/P-ERK signaling pathways. سامانه مدیریت نشریات علمی, 79(2), 367-377. doi: 10.32592/ARI.2024.79.2.367
Farinaz Jigari-Asl; Monireh Khordadmehr; Behzad baradaran; Elham Baghbani; Saeed Noorolyai; Shima Rahmani; Adel Saberivand. "Restoration of miR-451a-5p/miR-34a-5p could suppress the proliferation and migration of human breast cancer cells through Wnt/β- catenin and ERK/P-ERK signaling pathways". سامانه مدیریت نشریات علمی, 79, 2, 1403, 367-377. doi: 10.32592/ARI.2024.79.2.367
Jigari-Asl, Farinaz, Khordadmehr, Monireh, baradaran, Behzad, Baghbani, Elham, Noorolyai, Saeed, Rahmani, Shima, Saberivand, Adel. (1403). 'Restoration of miR-451a-5p/miR-34a-5p could suppress the proliferation and migration of human breast cancer cells through Wnt/β- catenin and ERK/P-ERK signaling pathways', سامانه مدیریت نشریات علمی, 79(2), pp. 367-377. doi: 10.32592/ARI.2024.79.2.367
Jigari-Asl, Farinaz, Khordadmehr, Monireh, baradaran, Behzad, Baghbani, Elham, Noorolyai, Saeed, Rahmani, Shima, Saberivand, Adel. Restoration of miR-451a-5p/miR-34a-5p could suppress the proliferation and migration of human breast cancer cells through Wnt/β- catenin and ERK/P-ERK signaling pathways. سامانه مدیریت نشریات علمی, 1403; 79(2): 367-377. doi: 10.32592/ARI.2024.79.2.367
Restoration of miR-451a-5p/miR-34a-5p could suppress the proliferation and migration of human breast cancer cells through Wnt/β- catenin and ERK/P-ERK signaling pathways
1Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, 51665-1647, Tabriz, Iran
2Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
3Immunology Research Center, Tabriz University of Medical Sciences, 51666-14761, Tabriz, Iran, and Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, 51666-14761, Tabriz, Iran
4Immunology Research Center, Tabriz University of Medical Sciences, 51666-14761, Tabriz, Iran
5Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, 51665-1647, Tabriz, Iran
چکیده
MicroRNAs (miRNAs) are a class of small non-coding RNAs of 21–25 nucleotides in length and display an essential role in regulating cancer initiation, development, and progression. Breast cancer (BC) is the most commonly detected malignancy in women, and it is one of the main motives of death worldwide. In this study, the impacts of microRNA-451a-5p and miR-34a-5p (tumor suppressors), individually and combined, transfections were conducted on the apoptosis, proliferation, and migration of breast cancer cells in vitro. For carrying out this research, malignant breast cancer cells (MDA-MB-231) were transfected with miR-451a-5p and miR-34a-5p mimics. Then, the cytotoxicity, apoptosis, proliferation, migration and, the protein and gene expression of caspase-3, caspase-8, MMP9, ROCK, vimentin, c-Myc of the cancer cells were assessed by MTT, flow cytometry, q-RT-PCR (expression levels of caspase-3, caspase-8, MMP9, ROCK, vimentin, c-Myc genes), wound healing, and western blot assays. The resluts indicated that the miR-34a-5p and miR-451a-5p could additionally induce apoptosis and cell cycle arrest in the sub-G1-phase, repress the proliferation and migration in the breast cancer cells, and could also decrease β- catenin, ERK/P-ERK protein expressions. The present data documented that restoring tumor suppressor miR-451/miR-34 in vitro strongly induced the programmed cell death and obviously inhibited the cell proliferation and migration in human breast cancer cells. Taken to gather, miR-451a and miR-34a have a considerable role in breast cancer cell proliferation and migration ability via Wnt/β-catenin and ERK/P-ERK signaling pathways. Therefore, the simultaneous restoration of the presented tumor suppressor miRNAs may be proposed as a valuable and potential therapeutic strategy in breast cancer treatment. However, further study should be meaningful.
بازگردانی miR-451a-5p/miR-34a-5p می تواند پرولیفراسیون و مهاجرت سلول های سرطان پستان را از طریق سیگنالینگ مسیرهای Wnt/β- catenin و ERK/P-ERK مهار کند
چکیده [English]
MicroRNA ها (miRNAs) دسته ای از RNA های کوچک غیر کدکننده با طول 21-25 نوکلئوتید هستند و نقش اساسی در تنظیم شروع، توسعه و پیشرفت سرطان دارند. سرطان پستان (BC) شایع ترین بدخیمی تشخیص داده شده در زنان است و یکی از علل اصلی مرگ در سراسر جهان است. در این مطالعه، اثرات microRNA-451a-5p و miR-34a-5p (سرکوب کنندههای تومور)، به صورت جداگانه و ترکیبی، به وسیله ترانسفکشنها بر آپوپتوز، تکثیر و مهاجرت سلولهای سرطان پستان در شرایط آزمایشگاهی انجام شد. برای انجام این تحقیق، سلولهای سرطانی بدخیم پستان (MDA-MB-231) با مقلدهای miR-451a-5p و miR-34a-5p ترانسفکت شدند. سپس سمیت سلولی، آپوپتوز، تکثیر، مهاجرت و بیان پروتئین و ژن کاسپاز-3، کاسپاز-8، MMP9، ROCK، ویمنتین، c-Myc سلول های سرطانی با استفاده از MTT، فلوسیتومتری، PCRکمی (سطح بیان ژن های کاسپاز-3، کاسپاز-8، MMP9، ROCK، ویمنتین، c-Myc)، ترمیم زخم و سنجش وسترن بلات بررسی شد. نتایج نشان دادند که miR-34a-5p و miR-451a-5p میتوانند آپوپتوز و توقف چرخه سلولی را در فاز فرعی G1 القا کنند، تکثیر و مهاجرت را در سلولهای سرطان سینه سرکوب کنند، و همچنین میتوانند β-کاتنین و بیان پروتئین ERK/P-ERK را کاهش دهند. بنابراین، miR-451a و miR-34a نقش قابل توجهی در تکثیر سلول های سرطان سینه و توانایی مهاجرت از طریق مسیرهای سیگنالینگ Wnt/β-catenin و ERK/P-ERK دارند. دادههای حاضر نشان میدهد که بازیابی سرکوبگر تومور miR-451/miR-34 در شرایط آزمایشگاهی به شدت باعث مرگ برنامهریزیشده سلولی شده و به طور مشخصی از تکثیر و مهاجرت سلولی در سلولهای سرطان سینه انسان جلوگیری میکند. بنابراین، ترنسفکشن همزمان miRNA های سرکوبگر تومور ارائه شده ممکن است به عنوان یک استراتژی درمانی ارزشمند و بالقوه در درمان سرطان پستان پیشنهاد شود. با این حال، مطالعه بیشتری باید در این زمینه انجام شود.
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