Lentiviral short hairpin RNA screen of human kinases and phosphatases to identify potential biomarkers in oral squamous cancer cells.

Abstract

Oral carcinoma is a serious public health problem and the leading cause of head and neck cancer mortality worldwide. Moreover, oral cancer patients often present symptoms at a late stage and show a high recurrence rate after treatment. Therefore, there is an urgent need to identify novel biomarkers for early diagnosis or clinical oral cancer therapy. In this study, we employed a subset of lentiviral short hairpin RNAs targeted against various kinases and phosphatases, designed by The RNAi Consortium, to screen systemically and in a high-throughput manner for potential growth regulators of oral cancer cells. The screen revealed a total of 50 candidate genes, for which more than 90% of growth inhibition in human oral squamous cancer HSC-3 cells was obtained. Furthermore, bioinformatic analysis of these candidate genes identified transforming growth factor-β receptor type II- and fms-related tyrosine kinase 3-related molecular pathways that are involved in NF-κB-mediated growth of HSC-3 cells. These candidate genes may be potential biomarkers for early diagnosis of oral cancer. In addition, these candidate genes represent potential targets for anticancer drug design helping to develop a personalized treatment to combat oral cancer.

• Authors: Ming-Han Yeh, Tzung-Chieh Tsai, Han-Peng Kuo, Nai-Wen Chang, Miao-Rong Lee, Jing-Gung Chung, Ming-Hsui Tsai, Jah-Yao Liu, Ming-Ching Kao
• Journal: International journal of oncology (Int J Oncol) Vol. 39 Issue 5 Pg. 1221-31 (Nov 2011) ISSN: 1791-2423 [Electronic] Greece
• PMID: 21720705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• NF-kappa B
• RNA, Small Interfering
• Receptors, Transforming Growth Factor beta
• SHC1 protein, human
• Shc Signaling Adaptor Proteins
• Src Homology 2 Domain-Containing, Transforming Protein 1
• Phosphotransferases
• FLT3 protein, human
• fms-Like Tyrosine Kinase 3
• Protein Serine-Threonine Kinases
• I-kappa B Kinase
• IKBKB protein, human
• Receptor, Transforming Growth Factor-beta Type II
• Phosphoric Monoester Hydrolases

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Squamous Cell (enzymology, genetics)
• Cell Line, Tumor
• Cell Proliferation
• Computational Biology
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genetic Vectors (genetics)
• High-Throughput Screening Assays
• Humans
• I-kappa B Kinase (metabolism)
• Lentivirus (genetics)
• Mouth Neoplasms (enzymology, genetics)
• NF-kappa B (metabolism)
• Phosphoric Monoester Hydrolases (genetics, metabolism)
• Phosphotransferases (genetics, metabolism)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Protein Transport
• RNA, Small Interfering (genetics)
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (antagonists & inhibitors)
• Reproducibility of Results
• Shc Signaling Adaptor Proteins (metabolism)
• Signal Transduction
• Src Homology 2 Domain-Containing, Transforming Protein 1
• fms-Like Tyrosine Kinase 3 (antagonists & inhibitors)