Genetics and epigenetics of cervix uteri of cancer

Cervical cancer is a predominant malignancy affecting women globally, with genetic and epigenetic factors playing crucial roles in its development. High-risk human papillomavirus (HPV) infection, particularly types ۱۶ and ۱۸, is the primary risk factor. Viral oncoproteins E۶ and E۷ disrupt tumor suppressor pathways, particularly TP۵۳ and RB۱, fostering uncontrolled cellular proliferation. In addition to genetic mutations, epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNA activity, also contribute to the disease. Hypermethylation of tumor suppressor genes, including CDKN۲A and RASSF۱A, leads to their silencing, facilitating cancer progression. Moreover, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play roles in regulating genes associated with cell proliferation, apoptosis, and metastasis. Understanding the genetic and epigenetic alterations in cervical cancer provides crucial insights into its pathogenesis and offers potential biomarkers for diagnosis and prognosis. Epigenetic therapies targeting DNA methylation and miRNAs are promising avenues for treatment, emphasizing the importance of continued research in this field. Cervical cancer represents a significant health challenge for women, particularly in low- and middle-income countries(۱). Its etiology is multifactorial, involving both genetic mutations and epigenetic modifications. The most significant genetic contributor is infection with high-risk HPV strains, notably types ۱۶ and ۱۸, which account for the majority of cervical cancer cases(۲). HPV oncoproteins E۶ and E۷ disrupt tumor suppressor genes TP۵۳ and RB۱, leading to cell cycle dysregulation and uncontrolled proliferation(۳). Beyond HPV, genetic mutations play a critical role. Alterations in genes such as MYC and KRAS intensify the malignancy's aggressiveness. For example, mutations in TP۵۳, often termed the "guardian of the genome," impair DNA repair mechanisms, increasing genomic instability and cancer progression. Epigenetic modifications further complicate cervical cancer pathogenesis(۴). DNA methylation, especially hypermethylation of tumor suppressor genes like CDKN۲A and RASSF۱A, leads to the silencing of these critical genes, a change commonly found in cervical cancer that correlates with poor prognosis. Histone modifications also affect chromatin structure, thereby influencing gene expression(۳, ۴). Non-coding RNAs, particularly microRNAs (miRNAs), play an increasingly recognized role in cervical cancer. MiRNAs, such as the miR-۳۴a, miR-۲۱, and miR-۲۰۰ families, impact pathways regulating cell growth and apoptosis. Additionally, long non-coding RNAs (lncRNAs)(۵), like MALAT۱ and HOTAIR, regulate chromatin dynamics and gene transcription, thus promoting metastasis and cancer progression(۴, ۵). Conclusion The development of cervical cancer is a complex process driven by both genetic mutations and epigenetic modifications. While HPV infection remains the primary risk factor, other genetic and epigenetic changes, such as DNA methylation and non-coding RNA activity, significantly contribute to the disease's pathogenesis. Advances in understanding these molecular mechanisms offer new opportunities for early diagnosis, targeted therapies, and personalized treatment strategies. Future research should prioritize translating these insights into clinical practice to improve outcomes for women with cervical cancer.

کلیدواژه ها:

human papillomavirus ، DNA methylation ، uterine cervical neoplasms