Long noncoding RNA DLEU1 aggravates pancreatic ductal adenocarcinoma carcinogenesis via the miR-381/CXCR4 axis.

Abstract

Recent evidence has highlighted that long noncoding RNAs (lncRNA) are associated with many diseases, particularly cancer. However, current understanding of the lncRNA deleted in lymphocytic leukemia 1 (DLEU1) in pancreatic ductal adenocarcinoma (PDAC) remains limited. Our studies indicated that the DLEU1 expression level was upregulated in PDAC tissue samples compared with adjacent normal tissue. Moreover, the aberrant overexpression of DLEU1 indicated poor prognosis of patients with PDAC. Loss-of-function experiments revealed that DLEU1 knockdown inhibited the proliferation, migration, and invasion of PDAC cells in vitro and decreased tumor growth in vivo. Bioinformatics analysis predicted that miR-381 potentially targeted the DLEU1 3'-untranslated region (UTR), suggesting an interaction between miR-381 and DLEU1. Furthermore, miR-381 also targeted the chemokine receptor-4 (CXCR4) messenger RNA 3'-UTR, which was validated by luciferase reporter assay. Taken together, our study demonstrated the oncogenic role of DLEU1 in clinical PDAC specimens and cellular experiments, showing the potential involvement of DLEU1/miR-381/CXCR4 pathway. These results provide novel insight into PDAC tumorigenesis.

• Authors: Song Gao, Yunyun Cai, Hu Zhang, Fei Hu, Lengchen Hou, Qing Xu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 5 Pg. 6746-6757 (05 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30382579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• CXCR4 protein, human
• DLEU1 lncRNA, human
• MIRN381 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Receptors, CXCR4
• Tumor Suppressor Proteins

Topics

• Adult
• Aged
• Carcinogenesis (genetics)
• Carcinoma, Pancreatic Ductal (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• Pancreatic Neoplasms (genetics)
• RNA, Long Noncoding (genetics)
• Receptors, CXCR4 (genetics)
• Tumor Suppressor Proteins (genetics)