title: Long non-coding RNA CRNDE promotes gallbladder carcinoma carcinogenesis and as a scaffold of DMBT1 and C-IAP1 complexes to activating PI3K-AKT pathway.
abstract: 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.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Yueqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Ni
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Ai
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Houbao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Yebo
authors.initials: Y
authors.lastname: Shao
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D062085:RNA, Long Noncoding; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C586983:CRNDE RNA, human; C108174:DMBT1 protein, human
keywords: CRNDE; GBC carcinogenesis; c-IAP1; migration and invasion; deleted in malignant brain tumors 1 (DMBT1)