The E3 ubiquitin ligase SIAH2 is a prosurvival factor overexpressed in oral cancer.
BACKGROUND
This study aimed at investigating the expression and functional significance of seven in absentia homologues 2 (SIAH2), an E3 ubiquitin ligase, in oral squamous cell carcinoma (OSCC).


METHODS
Comparative genomic hybridization and real-time PCR were performed to examine the amplification of SIAH2 gene in clinical specimens of OSCC tissues. Expression of SIAH2 mRNA and protein was examined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical assays, respectively. Apoptosis was examined by annexing V staining and Poly (ADP-ribose) polymerase (PARP) cleavage, with or without sienna-mediated SIAH2 knockdown. The expression of p53 was analyzed by immunoblotting.


RESULTS
Levels of SIAH2 DNA and mRNA were significantly greater in clinical OSCC specimens and in cultured OSCC cells, which also stained positively for the SAIH2 protein. Knockdown of SIAH2 led to growth suppression and apoptosis induction in a p53-independent mechanism.


CONCLUSIONS
These results revealed a tight correlation of SIAH2 overexpression with OSCC and suggest an oncogenic role of SIAH2 in oral cancer.
Department of Biological Science and Technology, China Medical University, 91 Hsueh-Shih Rd., Taichung 404, Taiwan, R.O.C. linjh@mail.cmu.edu.tw.
Shu-Chen
SC
Hsieh
Sheng-Nan
SN
Kuo
Yi-Han
YH
Zheng
Ming-Hsui
MH
Tsai
Yu-Sheng
YS
Lin
Ju-Hwa
JH
Lin
D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
Oral cancer; Siah2; apoptosis; ubiquitin ligase