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

• Published in: International journal of oncology Vol. 39; no. 5; pp. 1221 - 1231
• Main Authors: YEH, Ming-Han, TSAI, Tzung-Chieh, KUO, Han-Peng, CHANG, Nai-Wen, LEE, Miao-Rong, CHUNG, Jing-Gung, TSAI, Ming-Hsui, LIU, Jah-Yao, KAO, Ming-Ching
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.11.2011
• Subjects: Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - enzymology; Carcinoma, Squamous Cell - genetics; Cell Line, Tumor; Cell Proliferation; Computational Biology; fms-Like Tyrosine Kinase 3 - antagonists & inhibitors; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genetic Vectors - genetics; High-Throughput Screening Assays; Humans; I-kappa B Kinase - metabolism; Lentivirus - genetics; Medical sciences; Mouth Neoplasms - enzymology; Mouth Neoplasms - genetics; NF-kappa B - metabolism; Otorhinolaryngology. Stomatology; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Phosphotransferases - genetics; Phosphotransferases - metabolism; Protein Transport; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Receptors, Transforming Growth Factor beta - antagonists & inhibitors; Reproducibility of Results; RNA, Small Interfering - genetics; Shc Signaling Adaptor Proteins - metabolism; Signal Transduction; Src Homology 2 Domain-Containing, Transforming Protein 1; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; RNA interference; Oral cancer; Phosphoprotein phosphatase; Biological marker; Phosphoric monoester hydrolases; phosphoprotein phosphatases; Esterases; Cancerology; kinases; Human; Squamous cell carcinoma; Enzyme; Stomatology; Transferases; biomarkers; Retroviridae; Malignant tumor; Medical screening; Lentivirus; Virus; Gene silencing; high-throughput screening assays; Kinase; Hydrolases; Oral cavity disease; Short hairpin RNA; Cancer
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2011.1100

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.