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Translation regulatory factor RBM3 is a proto-oncogene that prevents mitotic catastrophe.
- Source :
-
Oncogene [Oncogene] 2008 Jul 31; Vol. 27 (33), pp. 4544-56. Date of Electronic Publication: 2008 Apr 21. - Publication Year :
- 2008
-
Abstract
- RNA-binding proteins play a key role in post-transcriptional regulation of mRNA stability and translation. We have identified that RBM3, a translation regulatory protein, is significantly upregulated in human tumors, including a stage-dependent increase in colorectal tumors. Forced RBM3 overexpression in NIH3T3 mouse fibroblasts and SW480 human colon epithelial cells increases cell proliferation and development of compact multicellular spheroids in soft agar suggesting the ability to induce anchorage-independent growth. In contrast, downregulating RBM3 in HCT116 colon cancer cells with specific siRNA decreases cell growth in culture, which was partially overcome when treated with prostaglandin E(2), a product of cyclooxygenase (COX)-2 enzyme activity. Knockdown also resulted in the growth arrest of tumor xenografts. We have also identified that RBM3 knockdown increases caspase-mediated apoptosis coupled with nuclear cyclin B1, and phosphorylated Cdc25c, Chk1 and Chk2 kinases, implying that under conditions of RBM3 downregulation, cells undergo mitotic catastrophe. RBM3 enhances COX-2, IL-8 and VEGF mRNA stability and translation. Conversely, RBM3 knockdown results in loss in the translation of these transcripts. These data demonstrate that the RNA stabilizing and translation regulatory protein RBM3 is a novel proto-oncogene that induces transformation when overexpressed and is essential for cells to progress through mitosis.
- Subjects :
- Animals
Cell Cycle Proteins genetics
Cell Cycle Proteins metabolism
Cell Transformation, Neoplastic genetics
Colonic Neoplasms genetics
Cyclooxygenase 2 genetics
Cyclooxygenase 2 metabolism
Dinoprostone genetics
Dinoprostone metabolism
Female
Fibroblasts metabolism
HeLa Cells
Humans
Interleukin-8 genetics
Interleukin-8 metabolism
Mice
Mice, Nude
NIH 3T3 Cells
Neoplasm Transplantation
Proto-Oncogene Mas
Proto-Oncogene Proteins genetics
RNA, Messenger genetics
RNA, Neoplasm genetics
RNA-Binding Proteins genetics
Spheroids, Cellular metabolism
Vascular Endothelial Growth Factor A genetics
Vascular Endothelial Growth Factor A metabolism
Cell Transformation, Neoplastic metabolism
Colonic Neoplasms metabolism
Mitosis genetics
Protein Biosynthesis genetics
Proto-Oncogene Proteins metabolism
RNA Stability genetics
RNA, Messenger metabolism
RNA, Neoplasm metabolism
RNA-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 27
- Issue :
- 33
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 18427544
- Full Text :
- https://doi.org/10.1038/onc.2008.97