Abstract 5124: Dynamic subcellular localization of the EMT-associated lncRNA lncX in pancreatic cancer

Abstract Long non-coding RNAs (lncRNAs) are non-coding RNAs that are longer than 200 nucleotides. These RNAs play essential regulatory roles in processes such as chromatin modification, transcriptional regulation, and protein localization, depending on their subcellular distribution in the nucleus or cytoplasm. These functions have attracted considerable attention in cancer research. LncX, highly expressed in various cancers, has been implicated in promoting tumor malignancy by influencing processes such as proliferation, epithelial-mesenchymal transition (EMT). It has been reported that lncX regulates mRNA by acting as a competing endogenous RNA through binding to miRNAs. However, the subcellular localization of lncX and its interactions with specific proteins in pancreatic ductal adenocarcinoma (PDAC) remain poorly understood. We investigated the localization of lncX in the PDAC cell lines using RNA fluorescence in situ hybridization (RNA-FISH) and super-resolution microscopy. Under conditions where cells were tightly adhered to one another, lncX was localized at the cell membrane. Interestingly, when cell adhesion was disrupted and the cells entered a suspended state, lncX predominantly localized in the nucleus and cytoplasm. A similar localization pattern was observed in PDAC samples from a PDAC mouse model (KPC) and human PDAC tissues. Notably, lncX co-localized with CDH1 at the cell membrane and translocated to the nucleus following specific stimuli. These findings suggest that lncX may play distinct roles depending on its localization, potentially contributing to cancer malignancy. Citation Format: Shu Hirako, Keiko Shinjo, Miho Suzuki, Tatsunori Nishimura, XingXing Wang, Yoshiteru Murofushi, Shinji Mii, Reo Maruyama, Kohei Kumegawa, Atsushi Enomoto, Yutaka Kondo. Dynamic subcellular localization of the EMT-associated lncRNA lncX in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5124.