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Abstract
Numerous long noncoding RNAs (lncRNAs) are aberrantly expressed in pancreatic cancer (PC); however, their functions and mechanisms in cancer progression are largely unknown. In this study, we identified a novel PC-associated lncRNA, RUNX1-IT1, that was significantly upregulated in PC patient samples from multiple centers and associated with poor prognosis. In vitro and in vivo, alterations in RUNX1-IT1 expression markedly affected PC proliferation, migration and invasion. RUNX1-IT1 contributed to the progression of PC by interacting with the adjacent gene RUNX1. Rescue experiments showed that RUNX1 reduced the cancer-promoting effect of RUNX1-IT1. RNA-seq analysis after silencing RUNX1-IT1 and RUNX1 highlighted alterations in the common target C-FOS. Mechanistically, we demonstrated that RUNX1-IT1 was a trans-acting factor that participated in the proliferation, migration and invasion of PC by recruiting RUNX1 to the C-FOS gene promoter. Furthermore, RUNX1-IT1 enhanced the transcription of the RUNX1 gene, indicating its potential as a cis-regulatory RNA involved in the upstream regulation of RUNX1. Overall, RUNX1-IT1 is a crucial oncogenic lncRNA that activates C-FOS expression by regulating and recruiting RUNX1 and is a potential prognostic biomarker and therapeutic target for PC.
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1 Third Military Medical University (Army Medical University), Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Chongqing, P. R. China (GRID:grid.410570.7) (ISNI:0000 0004 1760 6682)
2 University of Chinese Academy of Sciences, Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, P. R. China (GRID:grid.410570.7)
3 Southern Medical University, Department of First Hepatobiliary Surgery, Zhujiang Hospital, Guangzhou, P. R. China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471)
4 Third Military Medical University (Army Medical University), Department of Obstetrics and Gynecology, Southwest Hospital, Chongqing, P. R. China (GRID:grid.410570.7) (ISNI:0000 0004 1760 6682)
5 Third Military Medical University (Army Medical University), Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Chongqing, P. R. China (GRID:grid.410570.7) (ISNI:0000 0004 1760 6682); University of Chinese Academy of Sciences, Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing, P. R. China (GRID:grid.410570.7)