Research Papers:

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

Sheng Shen, Han Liu, Yueqi Wang, Jiwen Wang, Xiaolin Ni, Zhilong Ai, Hongtao Pan, Houbao Liu and Yebo Shao _

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Oncotarget. 2016; 7:72833-72844. https://doi.org/10.18632/oncotarget.12023

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Sheng Shen1,*, Han Liu1,*, Yueqi Wang1,*, Jiwen Wang1, Xiaolin Ni1, Zhilong Ai1, Hongtao Pan1, Houbao Liu1, Yebo Shao1

1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China

*These authors contributed equally to this work

Correspondence to:

Houbao Liu, email: [email protected]

Yebo Shao, email: [email protected]

Keywords: Deleted in malignant brain tumors 1 (DMBT1), CRNDE, c-IAP1, migration and invasion, GBC carcinogenesis

Received: June 20, 2016     Accepted: September 05, 2016     Published: September 14, 2016


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.

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