Department of Pharmaceutical Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, India.
Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, Uttarakhand 248007, India.
Pathol Res Pract. 2024 Oct;262:155570. doi: 10.1016/j.prp.2024.155570. Epub 2024 Aug 29.
Long non-coding RNAs (lncRNAs) have been identified as important participants in several biological functions, particularly their complex interactions with the KRAS pathway, which provide insights into the significant roles lncRNAs play in cancer development. The KRAS pathway, a central signaling cascade crucial for cell proliferation, survival, and differentiation, stands out as a key therapeutic target due to its aberrant activation in many human cancers. Recent investigations have unveiled a myriad of lncRNAs, such as H19, ANRIL, and MEG3, intricately modulating the KRAS pathway, influencing both its activation and repression through various mechanisms, including epigenetic modifications, transcriptional regulation, and post-transcriptional control. These lncRNAs function as fine-tuners, delicately orchestrating the balance required for normal cellular function. Their dysregulation has been linked to the development and progression of multiple malignancies, including lung, pancreatic, and colorectal carcinomas, which frequently harbor KRAS mutations. This scrutiny delves into the functional diversity of specific lncRNAs within the KRAS pathway, elucidating their molecular mechanisms and downstream effects on cancer phenotypes. Additionally, it underscores the diagnostic and prognostic potential of these lncRNAs as indicators for cancer detection and assessment. The complex regulatory network that lncRNAs construct within the context of the KRAS pathway offers important insights for the creation of focused therapeutic approaches, opening new possibilities for precision medicine in oncology. However, challenges such as the dual roles of lncRNAs in different cancer types and the difficulty in therapeutically targeting these molecules highlight the ongoing debates and need for further research. As ongoing studies unveil the complexities of lncRNA-mediated KRAS pathway modulation, the potential for innovative cancer interventions becomes increasingly promising.
长链非编码 RNA（lncRNA）已被确定为多种生物学功能的重要参与者，特别是它们与 KRAS 途径的复杂相互作用，这为 lncRNA 在癌症发展中所起的重要作用提供了深入了解。KRAS 途径是细胞增殖、存活和分化的中央信号级联，是一个关键的治疗靶点，因为在许多人类癌症中它会发生异常激活。最近的研究揭示了许多 lncRNA，如 H19、ANRIL 和 MEG3，它们通过多种机制（包括表观遗传修饰、转录调控和转录后控制）错综复杂地调节 KRAS 途径，影响其激活和抑制。这些 lncRNA 作为微调器，通过精细地协调正常细胞功能所需的平衡来发挥作用。它们的失调与多种恶性肿瘤的发生和进展有关，包括肺癌、胰腺癌和结直肠癌，这些癌症经常存在 KRAS 突变。这项研究深入探讨了 KRAS 途径中特定 lncRNA 的功能多样性，阐明了它们的分子机制以及对癌症表型的下游影响。此外，它强调了这些 lncRNA 作为癌症检测和评估指标的诊断和预后潜力。lncRNA 在 KRAS 途径中构建的复杂调控网络为有针对性的治疗方法的创建提供了重要的见解，为肿瘤学中的精准医学开辟了新的可能性。然而，lncRNA 在不同癌症类型中的双重作用以及治疗靶向这些分子的困难等挑战突显了正在进行的争论和进一步研究的必要性。随着正在进行的研究揭示 lncRNA 介导的 KRAS 途径调节的复杂性，创新的癌症干预措施的潜力变得越来越有希望。
