Huang Peng, Wen Feng, Li Qiu
Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Pharmacol. 2024 Jul 25;15:1432490. doi: 10.3389/fphar.2024.1432490. eCollection 2024.
Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied transcription factor, mediates multiple malignant behaviors by regulating cell cycle progression, tumor metastasis, and therapeutic response. Emerging evidence suggests that lncRNAs play a pivotal role in regulating the E2F1 pathway. This review aims to elucidate the intricate gene regulatory programs between lncRNAs and E2F1 in cancer progression. We elaborate on distinct mechanistic networks involved in cancer progression, emphasizing the potential of the lncRNAs/E2F1 axes as promising targets for cancer therapy. Additionally, we provide novel perspectives on current evidence, limitations, and future directions for targeting lncRNAs in human cancers. Fully deciphering the intricate network of lncRNA/E2F1-mediated regulatory mechanisms in cancer could facilitate the translation of current findings into clinical course, such efforts ultimately significantly improve the clinical prognosis of cancer patients.
长链非编码RNA(lncRNAs)构成了一类独特的RNA分子亚群,其蛋白质编码潜力有限,却对各种生物学活动产生关键影响。在癌症背景下,失调的lncRNAs作为重要调节因子,影响肿瘤的起始和恶性进展。这些lncRNAs通过吸附微小RNA并调节靶基因的表达,充当竞争性内源RNA(ceRNAs)。此外,它们还直接与RNA结合蛋白结合,可整合到一个复杂的机制网络中。E2F1是一种经过广泛研究的转录因子,通过调节细胞周期进程、肿瘤转移和治疗反应来介导多种恶性行为。新出现的证据表明,lncRNAs在调节E2F1通路中起关键作用。本综述旨在阐明癌症进展过程中lncRNAs与E2F1之间复杂的基因调控程序。我们详细阐述了参与癌症进展的不同机制网络,强调了lncRNAs/E2F1轴作为有前景的癌症治疗靶点的潜力。此外,我们针对目前在人类癌症中靶向lncRNAs的证据、局限性和未来方向提供了新的观点。全面解读癌症中lncRNA/E2F1介导的调控机制的复杂网络,有助于将当前的研究结果转化为临床实践,这些努力最终将显著改善癌症患者的临床预后。