Long non-coding RNA CRNDE promotes gallbladder carcinoma carcinogenesis and as a scaffold of DMBT1 and C-IAP1 complexes to activating PI3K-AKT pathway

Deleted in malignant brain tumors 1 (DMBT1) is deleted during cancer progression and as a potential tumor-suppressor gene in various types of cancer. However, its role in Gallbladder cancer remains poorly understood. DMBT1 has low-expression and deletion of copy number were detected in normal tissue...

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Bibliographic Details
Published in:Oncotarget 2016-11, Vol.7 (45), p.72833-72844
Main Authors: Shen, Sheng, Liu, Han, Wang, Yueqi, Wang, Jiwen, Ni, Xiaolin, Ai, Zhilong, Pan, Hongtao, Liu, Houbao, Shao, Yebo
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cell Movement - genetics
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Gallbladder Neoplasms - genetics
Gallbladder Neoplasms - metabolism
Gallbladder Neoplasms - mortality
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Inhibitor of Apoptosis Proteins - metabolism
Male
Mice
Phosphatidylinositol 3-Kinases - metabolism
Prognosis
Protein Binding
Proto-Oncogene Proteins c-akt - metabolism
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Research Paper
RNA Stability
RNA, Long Noncoding - genetics
Signal Transduction
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Summary:Deleted in malignant brain tumors 1 (DMBT1) is deleted during cancer progression and as a potential tumor-suppressor gene in various types of cancer. However, its role in Gallbladder cancer remains poorly understood. DMBT1 has low-expression and deletion of copy number were detected in normal tissues and GBC cancer tissues by qRT-PCR. Knockdown of DMBT1 increased migration and invasion and overexpressed DMBT1 impaired migration and invasion in GBC cells. We also evaluated the molecular mechanism of DMBT1 by RNA sequencing and GSEA analysis. RNA-Pulldown and RIP assay authenticated CRNDE can specified binding with DMBT1 and c-IAP1. Downregulation of DMBT1 resulted in significant change of gene expression (at least 2-fold) in PI3K-AKT pathway, increased expression of MMP-9, JUK-1, ERK and AKT, activating PI3K-AKT pathway lead to GBC carcinogenesis.We for the first time reported, DMBT1 as a prognosis biomarker, is low-expressed in GBC tumors, and CRNDE act as a scaffold to recruit the DMBT1 and c-IAP1, promotes the PI3K-AKT pathway. Our study reveals DMBT1 may be an important contributor to GBC cancer development.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.12023