Heterogeneous nuclear ribonucleoprotein G shows tumor suppressive effect against oral squamous cell carcinoma cells.
OBJECTIVE
Heterogeneous nuclear ribonucleoproteins (hnRNP) are nucleic acid binding proteins involved in RNA processing. We found that hnRNP G is expressed in normal human oral epithelial cells while frequently not found in the cells derived from human oral squamous cell carcinomas (HOSCC). The current study was designed to test the hypothesis that hnRNP G is a tumor suppressor.


METHODS
We investigated the expression levels of hnRNP G protein in normal, precancerous, and malignant oral tissues by in situ immunohistochemistry. In addition, wild-type or mutant hnRNP G was ectopically overexpressed in HOSCC cells and their effects on cellular replication kinetics, colonogenic efficiency, anchorage-independent growth, and in vivo tumorigenicity were determined.


RESULTS
In situ immunohistochemical staining showed robust presence of hnRNP G in the basal cell layers of normal oral epithelium but the level of its staining was markedly reduced in dysplastic or cancerous tissues. Ectopic expression of wild-type hnRNP G in cancer cells lacking hnRNP G expression or containing mutant hnRNP G resulted in severe retardation of proliferation, reduction of colonogenic efficiency, loss of anchorage-independent growth, and reduction of in vivo tumorigenicity in immunocompromised mice. In addition, hnRNP G overexpression led to up-regulation of the expression of TXNIP, a cell cycle inhibitory gene, and significantly reduced the expression of the genes that promote cellular proliferation, such as EGR1, JUND, JUNB, FOS, FOSL1, ROS, and KIT.


CONCLUSIONS
These results indicate that hnRNP G is a tumor suppressor against HOSCC but its mechanisms of action remain to be further investigated.
Shin
Ki-Hyuk
KH
School of Dentistry, University of California, Los Angeles, California 90095-1668, USA.
Kang
Mo K
MK
Kim
Reuben H
RH
Christensen
Russell
R
Park
No-Hee
NH
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000503:physiopathology; D002448:Cell Adhesion; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D051379:Mice; D009062:Mouth Neoplasms / Q000235:genetics* / Q000503:physiopathology; D011230:Precancerous Conditions; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D034441:Heterogeneous-Nuclear Ribonucleoproteins; C510272:RBMX protein, human