خاموش شدن ژن به روش اپی ژنتیک در شروع و پیشرفت سرطان کولورکتال

نوع مقاله : مقاله مروری

نویسندگان

مرکز تحقیقات بیماری های غیر واگیر، دانشگاه علوم پزشکی جهرم، جهرم، ایران

چکیده

مقدمه: سرطان کولورکتال (colorectal cancer, CRC)، سومین سرطان شاخته شده و چهارمین علت منجر به مرگ در دنیاست. این بیماری حاصل مراحل مختلفی است که باعث انباشته شدن تعدیلات ژنتیک و اپی ژنتیک در ژن های سرکوب کننده سرطان و ژن های سرطان زا می شود. تعدیلات اپی ژنتیک، یک نقش اساسی در تنظیم نسخه برداری و بیان ژن بازی می کنند. این تعدیلات شامل متیلاسیون DNA در نواحی پروموتر (promoter) ژن، تعدیلات هیستون و مداخلات RNA غیر کدشونده (non‐coding RNA) است. تعدیلات هیستون و متیلاسیون DNA یک ترکیب دخیل در خاموش شدن ژن ها هستند که منجر به تومورزایی می شوند. متیلاسیون DNA، بوسیله آنزیم های DNA متیل ترانس فراز(DNA methyltransferases, DNMTs) که گروه متیل را به اس-آدنوزین متیونین به منظور الگوی متیلاسیون ژنومی و خاموش شدن ژن منتقل می کنند انجام می شود. در این تحقیق، ما در باره اطلاعات رایج در حال رشد مربوط به مداخله هایپرمتیلاسیون چندین ژن سرکوب کننده سرطان و مکانسیم مولکولی آنها در سرطان کولورکتال بحث می کنیم. روش ها: برای این مقاله مروری، مطالعات قابل قبول با استفاده از PubMed, SCOPUS, NCBI  و Ovid database و با انتخاب کلمات کلیدی لازم از فهرست MeSH (Medical Subject Headings) بدست آمد. یافته ها: ما دریافتیم که آنزیم های DNA متیل ترانس فراز می توانند باعث متیلاسیون ژن های سرکوب کننده سرطان و در نتیجه القاء سرطان گردند. نتیجه: کاهش بیان ژن های سرکوب کننده سرطان باعث القاء سرطان می گردد.

کلیدواژه‌ها

عنوان مقاله [English]

Epigenetic gene silencing in colorectal cancer initiation and progression, review article

نویسندگان [English]

  • Fraidoon Kavoosi
  • Masumeh Sanaei
Research center for non-communicable diseases, Jahrom University of medical sciences, Jahrom, Iran
چکیده [English]

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth cause of cancer death worldwide. It develops through multiple steps that results from the progressive accumulation of mutations and epigenetic modifications in tumor suppressor genes (TSGs) and oncogenes. Epigenetic modifications play a fundamental role in the regulation and transcription of gene expression. These modifications involve DNA methylation of promoter regions, histone modifications, and non‐coding RNAs (ncRNAs) interventions. Histone modification and DNA methylation are involved in a complex network to maintain gene silencing lead to tumorigenesis. DNA methylation is methylated by DNA methyltransferases (DNMTs), which transfer the methyl group from S-adenosylmethionine (SAM) to generate patterns of genomic methylation that silence genes. In this review, we discuss the current and fast-growing knowledge about the contribution of the hypermethylation of several TSGs toward an understanding of molecular mechanisms of CRC. Methods. For this review article, the eligible studies were obtained by searching PubMed, SCOPUS, NCBI, and Ovid database with the MeSH terms combined with free terms. Results. We found evidence that DNA methyltransferases can induce DNA methylation in tumor suppressor genes (TSGs) resulting in cancer induction. Conclusion. The downregulation of TSGs expression might be responsible in promoting cancer induction.

کلیدواژه‌ها [English]

  • Epigenetics
  • Methylation
  • Gene expression
  • Colorectal cancer

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مجله دانشکده پزشکی دانشگاه علوم پزشکی مشهد
دوره 64، شماره 4
مهر و آبان 1400
صفحه 3416-3426

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