Genome-Wide Transcriptome Profiling of the Neoplastic Giant Cell Tumor of Bone Stromal Cells by RNA Sequencing
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摘要Giant cell tumor of bone (GCTB) is the most common non-malignant primary bone tumor reported in Hong Kong. Failure of treatment in advanced GCTB with aggressive local recurrence remains a clinical challenge. In order to reveal the molecular mechanism underlying the pathogenesis of this tumor, we aimed to examine the transcriptome profiling of the neoplastic stromal cells of GCTB in this study. RNA-sequencing was performed on three GCTB stromal cell samples and one bone marrow-derived MSC sample and 174 differentially expressed genes (DEGs) were identified between these two cell types. The top five up-regulated genes are SPP1, F3, TSPAN12, MMP13, and LGALS3BP and further validated by qPCR and Western Blotting. Knockdown of SPP1 was found to induce RUNX2 and OPG expression in GCTB stromal cells but not the MSCs. Ingenuity pathway analysis (IPA) of the 174 DEGs revealed significant alternations in 23 pathways; variant calling analysis revealed 1915 somatic variants of 384 genes with high or moderate impacts. Interestingly, four canonical pathways were found overlapping in both analyses; from which VEGFA, CSF1, PLAUR, and F3 genes with somatic mutation were found up-regulated in GCTB stromal cells. The STRING diagram showed two main clusters of the DEGs; one cluster of histone genes that are down-regulated in GCTB samples and another related to osteoblast differentiation, angiogenesis, cell cycle progression, and tumor growth. The DEGs and somatic mutations found in our study warrant further investigation and validation, nevertheless, our study add new insights in the search for new therapeutic targets in treating GCTB.
著者Lau CP, Kwok JS, Tsui JC, Huang L, Yang KY, Tsui SK, Kumta SM
期刊名稱Journal of Cellular Biochemistry
出版年份2017
月份6
卷號118
期次6
出版社Wiley Periodicals, Inc.
頁次1349 - 1360
國際標準期刊號0730-2312
電子國際標準期刊號1097-4644
語言英式英語
關鍵詞DIFFERENTIALLY EXPRESSED GENES, GIANT CELL TUMOR OF BONE, OSTEOPONTIN, RNA SEQUENCING, SOMATIC MUTATIONS

上次更新時間 2021-24-02 於 01:34