Shi Mengmeng, Zhang Rui, Lyu Hao, Xiao Shuai, Guo Dong, Zhang Qi, Chen Xing-Zhen, Tang Jingfeng, Zhou Cefan
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China.
Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2R3, Canada.
J Adv Res. 2025 Feb 9. doi: 10.1016/j.jare.2025.02.001.
The invasion and metastasis of pancreatic cancer (PC) are key factors contributing to disease progression and poor prognosis. This process is primarily driven by EMT, which has been the focus of recent studies highlighting the role of long non-coding RNAs (lncRNAs) as crucial regulators of EMT. However, the mechanisms by which lncRNAs influence invasive metastasis are multifaceted, extending beyond EMT regulation alone.
This review primarily aims to characterize lncRNAs affecting invasion and metastasis in pancreatic cancer. We summarize the regulatory roles of lncRNAs across multiple molecular pathways and highlight their translational potential, considering the implications for clinical applications in diagnostics and therapeutics.
The review focuses on three principal scientific themes. First, we primarily summarize lncRNAs orchestrate various signaling pathways, such as TGF-β/Smad, Wnt/β-catenin, and Notch, to regulate molecular changes associated with EMT, thereby enhancing cellular motility and invasivenes. Second, we summarize the effects of lncRNAs on autophagy and ferroptosis and discuss the role of exosomal lncRNAs in the tumor microenvironment to regulate the behavior of neighboring cells and promote cancer cell invasion. Third, we emphasize the effects of RNA modifications (such as mA and mC methylation) on stabilizing lncRNAs and enhancing their capacity to mediate invasive metastasis in PC. Lastly, we discuss the translational potential of these findings, emphasizing the inherent challenges in using lncRNAs as clinical biomarkers and therapeutic targets, while proposing prospective research strategies.
胰腺癌（PC）的侵袭和转移是导致疾病进展和预后不良的关键因素。这一过程主要由上皮-间质转化（EMT）驱动，EMT一直是近期研究的重点，这些研究强调了长链非编码RNA（lncRNAs）作为EMT关键调节因子的作用。然而，lncRNAs影响侵袭转移的机制是多方面的，不仅仅局限于EMT调节。
本综述主要旨在描述影响胰腺癌侵袭和转移的lncRNAs。我们总结了lncRNAs在多个分子途径中的调节作用，并突出其转化潜力，同时考虑其在诊断和治疗临床应用中的意义。
本综述聚焦于三个主要科学主题。首先，我们主要总结lncRNAs如何协调各种信号通路，如转化生长因子-β/ Smad、Wnt/β-连环蛋白和Notch信号通路，以调节与EMT相关的分子变化，从而增强细胞运动性和侵袭性。其次，我们总结lncRNAs对自噬和铁死亡的影响，并讨论外泌体lncRNAs在肿瘤微环境中调节邻近细胞行为和促进癌细胞侵袭的作用。第三，我们强调RNA修饰（如mA和mC甲基化）对lncRNAs稳定性的影响以及增强其在胰腺癌中介导侵袭转移的能力。最后，我们讨论这些发现的转化潜力，强调将lncRNAs用作临床生物标志物和治疗靶点所面临的固有挑战，同时提出前瞻性研究策略。
