LINC00346 promotes pancreatic cancer progression through the CTCF-mediated Myc transcription

• Published in: Oncogene Vol. 38; no. 41; pp. 6770 - 6780
• Main Authors: Peng, Wan-Xin, He, Rong-Zhang, Zhang, Ziqiang, Yang, Liu, Mo, Yin-Yuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.10.2019; Nature Publishing Group
• Subjects: 13/106; 45/41; 631/67/395; 631/80/83; Adenocarcinoma; Apoptosis; Biological markers; Biomarkers, Tumor - metabolism; c-Myc protein; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Care and treatment; CCCTC-Binding Factor - metabolism; CCCTC-Binding Factor - physiology; Cell Biology; Cell migration; Cell Proliferation; Development and progression; Disease Progression; Genetic aspects; Genetic transcription; Genomes; Human Genetics; Humans; Internal Medicine; Mass spectroscopy; Medicine; Medicine & Public Health; Myc protein; Neoplasm Invasiveness; Neoplasm Metastasis; Non-coding RNA; Oncology; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Phenotypes; Prognosis; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; RNA, Long Noncoding - physiology; Therapeutic applications; Transcription factors; Transcription, Genetic; Tumorigenesis
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-019-0918-z

Although multiple factors are known to contribute to pancreatic ductal adenocarcinoma (PDAC) progression, the role of long non-coding RNAs (lncRNAs) in PDAC remains largely unknown. In this study, we present data that long intergenic non-coding RNA 346 (LINC00346) functions as a promoting factor for PDAC development. We first show that LINC00346 is highly expressed in pancreatic tumor specimens as compared to normal pancreatic tissue based on interrogation of The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma dataset. Of significance, this upregulation of LINC00346 is associated with overall survival (OS) and disease-free survival (DFS), respectively. We further show that knockout (KO) of LINC00346 impairs pancreatic cancer cell proliferation, tumorigenesis, migration, and invasion ability. Importantly, these phenotypes can be restored by LINC00346 re-expression in KO cells (i.e., rescue experiment). RNA precipitation assays combined with mass spectrometry analysis indicate that LINC00346 interacts with CCCTC-binding factor (CTCF), a known transcriptional repressor of c-Myc. This interaction between LINC00346 and CTCF prevents the binding of CTCF to c-Myc promoter, relieving the CTCF-mediated repression of c-Myc. Thus, LINC00346 functions as a positive transcriptional regulator of c-Myc. Together, these results suggest that LINC00346 contributes to PDAC pathogenesis by activating c-Myc, and as such, LINC00346 may serve as a potential biomarker and therapeutic target for PDAC.