The lncRNA RUNX1-IT1 regulates C-FOS transcription by interacting with RUNX1 in the process of pancreatic cancer proliferation, migration and invasion

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...

Full description

Saved in:
Bibliographic Details
Published in:Cell death & disease 2020-06, Vol.11 (6), p.412-412, Article 412
Main Authors: Liu, Songsong, Zhang, Junfeng, Yin, Liangyu, Wang, Xianxing, Zheng, Yao, Zhang, Yujun, Gu, Jianyou, Yang, Ludi, Yang, Jiali, Zheng, Ping, Jiang, Yan, Shuai, Ling, Cai, Xiongwei, Wang, Huaizhi
Format: Article
Language:English
Subjects:
Animals
Base Sequence
c-Fos protein
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
Core Binding Factor Alpha 2 Subunit - metabolism
Disease Progression
Fos gene
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Mice, Nude
Neoplasm Invasiveness
Neoplasm Metastasis
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
Prognosis
Promoter Regions, Genetic - genetics
Protein Binding
Proto-Oncogene Proteins c-fos - genetics
Proto-Oncogene Proteins c-fos - metabolism
Ribonucleic acid
RNA
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
RNA-mediated interference
Runx1 protein
Therapeutic applications
Transcription
Transcription, Genetic
Up-Regulation - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-020-2617-7