Oral cancer is an important worldwide health problem. WHO predicts a continuing worldwide increase in the number of patients with oral cancer. In Taiwan, oral cavity cancer is also a critical health issue because it is the sixth leading cause of cancer death.
In this study, through collaborating with the RNAi Core of Academia Sinica, we used a large-scale RNAi approach to identify kinases and phosphatases that regulate cell survival in the human oral cancer HSC-3 cell line. A total of 6502 shRNA clones targeting to human kinases and phosphatases, covering 1236 genes with 737 kinases, 209 phosphatases and 30 dual function genes, were screened in this project. Lentivirus-shRNA constructs of these genes were used to infect HSC-3 cells and cell viabilities were assessed using CCK-8 Assay kit.
Amongst the 1236 genes, silencing of 51 genes were found to inhibit cell growth rate greater than 90%. We designated those genes as tumor growth promotion genes. Later, these growth promotion genes were analyzed by GeneGo software for their molecular pathway. We have obtained four putative pathways (IPP-1, TGF-beta receptor II, EGFR, and FLT-3) resulting from the GeneGo analysis, and TGF-beta receptor II may be the main pathway involved in cancer proliferation. Further studies are required to verify these candidate pathways and genes involved during oral oncogenesis. This study provides a systematic way to unravel the molecular mechanism leading to oral cancer and further finding for new targets for clinical oral cancer therapy.
