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J Transl Med. 2017 Jul 28;15(1):165. doi: 10.1186/s12967-017-1266-9.

Coiled-coil domain containing 109B is a HIF1α-regulated gene critical for progression of human gliomas.

Author information

1
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, #107 Wenhua Xi Road, Jinan, 250012, China.
2
Department of Neurosurgery, Jining No.1 People's Hospital, Jiankang Road, Jining, 272011, China.
3
Ningxia Key Laboratory of Craniocerebral Diseases, Incubation Base of the National Key Laboratory, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
4
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, #107 Wenhua Xi Road, Jinan, 250012, China. lixg@sdu.edu.cn.
5
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, #107 Wenhua Xi Road, Jinan, 250012, China. jian.wang@uib.no.
6
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway. jian.wang@uib.no.

Abstract

BACKGROUND:

The coiled-coil domain is a structural motif found in proteins that participate in a variety of biological processes. Aberrant expression of such proteins has been shown to be associated with the malignant behavior of human cancers. In this study, we investigated the role of a specific family member, coiled-coil domain containing 109B (CCDC109B), in human gliomas.

METHODS AND RESULTS:

We confirmed that CCDC109B was highly expressed in high grade gliomas (HGG; WHO III-IV) using immunofluorescence, western blot analysis, immunohistochemistry (IHC) and open databases. Through Cox regression analysis of The Cancer Genome Atlas (TCGA) database, we found that the expression levels of CCDC109B were inversely correlated with patient overall survival and it could serve as a prognostic marker. Then, a serious of cell functional assays were performed in human glioma cell lines, U87MG and U251, which indicated that silencing of CCDC109B attenuated glioma proliferation and migration/invasion both in vitro and in vivo. Notably, IHC staining in primary glioma samples interestingly revealed localization of elevated CCDC109B expression in necrotic areas which are typically hypoxic. Moreover, small interfering RNA (siRNA) and specific inhibiters of HIF1α led to decreased expression of CCDC109B in vitro and in vivo. Transwell assay further showed that CCDC109B is a critical factor in mediating HIF1α-induced glioma cell migration and invasion.

CONCLUSION:

Our study elucidated a role for CCDC109B as an oncogene and a prognostic marker in human gliomas. CCDC109B may provide a novel therapeutic target for the treatment of human glioma.

KEYWORDS:

CCDC109B; Glioma; HIF1α; Invasion; Proliferation

PMID:
28754121
PMCID:
PMC5534085
DOI:
10.1186/s12967-017-1266-9
[Indexed for MEDLINE]
Free PMC Article

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