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Circ-ASH2L promotes tumor progression by sponging miR-34a to regulate Notch1 in pancreatic ductal adenocarcinoma

Authors
  • Chen, Yan1, 2
  • Li, Zhonghu3
  • Zhang, Mengyun4
  • Wang, Bo3
  • Ye, Jiaxin3
  • Zhang, Yang3
  • Tang, Di3
  • Ma, Dandan3
  • Jin, Weidong3
  • Li, Xiaowu1, 5
  • Wang, Shuguang1
  • 1 Southwest Hospital, Army Medical University, Hepatobiliary Surgery Institute, Chongqing, China , Chongqing (China)
  • 2 985 Hospital of PLA, Chongqing, Hepatobiliary Surgery Department, Chongqing, China , Chongqing (China)
  • 3 Central Theater Command General Hospital of PLA, Dept. general surgery, Hubei, China , Hubei (China)
  • 4 Central Theater Command general hospital of PLA, Department Rheumatology of Integrated Traditional Chinese and Western Medicine, Hubei, China , Hubei (China)
  • 5 Hepatobiliary Surgery & Carson International Cancer Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy Center Shenzhen University, Shenzhen, China , Shenzhen (China)
Type
Published Article
Journal
Journal of Experimental & Clinical Cancer Research
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 12, 2019
Volume
38
Issue
1
Identifiers
DOI: 10.1186/s13046-019-1436-0
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundCircular RNAs (circRNAs) have recently been shown to play important roles in different tumors. However, their detailed roles and regulatory mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not well understood. This study aimed to identify enriched circRNAs and detect their functions and mechanisms in PDAC cells and tissues.MethodscircRNA-ASH2L (circ-ASH2L) was identified by circRNA microarray studies based on previous studies, and further detected in PDAC cells and samples by qRT-PCR. The functions of circ-ASH2L were identified by transwell, EdU, cell cycle or Tube formation assays. The regulatory mechanisms of circ-ASH2L were explored by WB, RIP, FISH, dual-luciferase assays, RNA pulldown or other assays.ResultsWe identified a circRNA (circ-ASH2L) based on our previous studies, detected its expression in different malignant cells and found that circ-ASH2L was highly expressed in pancreatic cells or tumor tissues and correlated with tumor malignancy. Further studies revealed that circ-ASH2L promoted tumor invasion, proliferation and angiogenesis by regulating miR-34a, thus regulate Notch 1 expression. Circ-ASH2L served as a miRNA sponge for miR-34a and promoted tumor progression in vivo. Finally, we analyzed circ-ASH2L expression in clinical tissues and found that high circ-ASH2L expression was correlated with lymphatic invasion and TNM stage and was an independent risk factor for pancreatic patient survival.Conclusionscirc-ASH2L play an important role in tumor invasion, and high circ-ASH2L may be a useful marker of PDAC diagnosis or progression.

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