Long non-coding RNA CRNDE promotes gallbladder carcinoma carcinogenesis and as a scaffold of DMBT1 and C-IAP1 complexes to activating PI3K-AKT pathway.
Long non-coding RNA CRNDE promotes gallbladder carcinoma carcinogenesis and as a scaffold of DMBT1 and C-IAP1 complexes to activating PI3K-AKT pathway.
复制标题
长链非编码RNA CRNDE促进胆囊癌癌变并作为DMBT1和C-IAP1复合物的支架激活PI3K-AKT通路
DOI：
10.18632/oncotarget.12023
复制
发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Shao Y
中科院分区：
文献类型：
--
作者：
Shen S;Liu H;Wang Y;Wang J;Ni X;Ai Z;Pan H;Liu H;Shao Y
恶性脑肿瘤1（DMBT 1）在癌症进展过程中缺失，并在各种类型的癌症中作为潜在的肿瘤抑制基因。然而，其在胆囊癌中的作用仍然知之甚少。qRT-PCR检测结果显示DMBT 1在正常组织和GBC癌组织中呈低表达，拷贝数缺失。在GBC细胞中，敲低DMBT 1增加迁移和侵袭，过表达DMBT 1损害迁移和侵袭。我们还通过RNA测序和GSEA分析评估了DMBT 1的分子机制。经RNA-Pulldown和RIP试验验证的CRNDE可特异性结合DMBT 1和c-IAP 1。DMBT 1下调导致PI 3 K-AKT通路基因表达显著改变（至少2倍），MMP-9、JUK-1、ERK和AKT表达增加，激活PI 3 K-AKT通路导致GBC癌变。我们首次报道了DMBT 1作为一种预后生物标志物在GBC肿瘤中低表达，CRNDE作为一种支架募集DMBT 1和c-IAP 1，促进PI 3 K-AKT通路。我们的研究表明，DMBT 1可能是GBC癌症发展的重要贡献者。
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.