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HPV 诱导的宫颈癌中的信号通路:探索 RNA 调节的治疗潜力。

Signaling pathways in HPV-induced cervical cancer: Exploring the therapeutic promise of RNA modulation.

机构信息

Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

Department of Clinical Laboratory Science, College of Applied Medical Sciences, Al Quwayiyah, Shaqra University, Riyadh, Saudi Arabia; Department of Pharmaceutical Chemistry, Azad Institute of Pharmacy and Research, Lucknow, UP, India.

出版信息

Pathol Res Pract. 2024 Nov;263:155612. doi: 10.1016/j.prp.2024.155612. Epub 2024 Sep 25.

Abstract

Cervical cancer, originating from the epithelial tissue of the uterine cervix, constitutes the most commonly diagnosed malignancy among women worldwide. The predominant etiological factor underpinning cervical carcinogenesis is persistent infection with high-risk human papillomavirus (HPV) genotypes, notably HPV-16 and HPV-18. Oncoproteins encoded by high-risk HPV interfere with multiple essential cellular signaling cascades. Specifically, E5, E6, and E7 proteins disrupt the signaling pathways like p53, retinoblastoma tumor suppressor protein (pRB), The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK), and Wnt/β-catenin, promoting HPV-mediated carcinogenesis. This dysregulation disrupts cell cycle control, apoptosis, and metastasis through modulation of microRNAs (miRNA) and key cellular processes. The novel therapeutic interventions for HPV prevention and detection are fundamental to patient management. RNA-based treatment modalities offer the potential for manipulating critical pathways involved in cervical carcinogenesis. RNA therapeutics offer novel approaches to drug development by targeting intracellular genetic elements inaccessible to conventional modalities. Additional advantages include rapid design, synthesis, and a reduced genotoxic profile compared to DNA-based therapies. Despite beneficial attributes, system stability and efficient delivery remain critical parameters. This study assessed the intricate relationship between HPV, cervical cancer, and various signaling pathways. The study explores miRNAs' diagnostic and therapeutic potential, mall interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs)in cervical cancer management. The review highlights the prospect of RNA-targeted therapies to modulate specific cancer signaling pathways. This approach offers a novel strategy for cervical cancer treatment through precise regulation of cancer signaling. Future research should concentrate on developing RNA-targeted interventions to improve cervical cancer treatment outcomes through increased therapeutic efficacy and specificity.

摘要

宫颈癌源自子宫颈的上皮组织,是全球女性最常见的诊断恶性肿瘤。宫颈癌发生的主要病因是持续性高危型人乳头瘤病毒(HPV)感染,尤其是 HPV-16 和 HPV-18 型。高危型 HPV 编码的致癌蛋白干扰多种重要的细胞信号转导途径。具体而言,E5、E6 和 E7 蛋白破坏了 p53、视网膜母细胞瘤肿瘤抑制蛋白(pRB)、磷酸肌醇 3 激酶(PI3K)/蛋白激酶 B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)、表皮生长因子受体(EGFR)、丝裂原激活的蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)和 Wnt/β-连环蛋白等信号通路,促进 HPV 介导的癌变。这种失调通过调节 microRNAs(miRNA)和关键细胞过程,破坏细胞周期控制、凋亡和转移。针对 HPV 的新型预防和检测治疗干预措施是患者管理的基础。基于 RNA 的治疗方法为操纵宫颈癌发生过程中的关键途径提供了潜力。RNA 疗法通过靶向传统方法不可及的细胞内遗传元件,为药物开发提供了新方法。与 DNA 疗法相比,其具有快速设计、合成和降低遗传毒性等优点。尽管具有有益的特性,但系统稳定性和高效递送仍然是关键参数。本研究评估了 HPV、宫颈癌和各种信号通路之间的复杂关系。该研究探讨了 miRNA 在宫颈癌管理中的诊断和治疗潜力、小干扰 RNA(siRNA)和长链非编码 RNA(lncRNA)。本综述强调了 RNA 靶向治疗调节特定癌症信号通路的前景。这种方法通过精确调节癌症信号,为宫颈癌治疗提供了一种新策略。未来的研究应集中于开发 RNA 靶向干预措施,通过提高治疗效果和特异性来改善宫颈癌治疗结果。

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