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• Elucidates how lncRNAs regulate EMT in pancreatic cancer via TGF-β, Wnt, and Notch pathways. • Summarizes the effects of lncRNAs on autophagy during pancreatic cancer invasion. • Reviews the impact of lncRNAs on ferroptosis in the invasive progression of pancreatic cancer. • Explores the role of exosomal lncRNAs in modulating the tumor microenvironment to promote PC spread. • Discusses RNA modifications (m 6 A, m 5 C) that enhance lncRNA stability and function in PC. 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 m 6 A and m 5 C 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.
Shi et al. (Sun,) studied this question.