Our group is mainly focusing on the role of small RNAs in cancer development and drug resistance. Small RNA, particularly microRNA (miRNA), plays an important role in regulating gene expression at post-transcriptional level. Altered expression of specific miRNAs can cause diseases. Study of miRNA expression and function in cancer cells could contribute to greater understanding of how miRNAs are involved in cancer development and drug resistance, which may lead to identification of important diagnostic/ prognostic markers for clinical practice, as well as potential target molecules for development of targeted cancer treatment. A major effort of our previous work had focused on the identification of novel small RNAs, the documentation of miRNA expression patterns in several cancer types, and evaluation of their potential use in tumor classification and prognostication. Our current work primarily focuses on the functional roles of miRNAs along with other regulatory components in clinically relevant experimental systems. Several ongoing projects are briefly described below:
Molecular pathogenesis of Merkel cell carcinoma
Merkel cell carcinoma (MCC) is an aggressive and lethal type of skin cancer, which is frequently infected by Merkel cell polyomavirus (MCPyV). However the molecular mechanism by which the virus induces tumorigenesis remains unclear. We identify specific miRNAs associated with MCPyV status, tumor metastasis and disease-specific survival in MCC patients, suggesting the importance of miRNAs in MCC development and progression. In this project, we aim to understand the functional roles of viral oncoproteins and miRNAs in MCC, and to identify biomarkers related to MCC development and progression.
Role and mechanism of miRNA regulation in drug resistance
Many human cancers are commonly initiated by activating mutations in kinases, which contribute to cancer development. This has prompted to the development of kinase inhibitors for blocking the oncogenic process. These small molecule inhibitors bind and inhibit kinase activity of specific kinases. Although kinase inhibitors have been used as specific targeted therapy for selected malignancies and have markedly improved patient outcomes, development of acquired kinase inhibitor resistance remains a major clinical challenge. Identifying the mechanisms of kinase inhibitor resistance is warranted to improve the effectiveness of these therapies and patient outcome. The aim of this project is to investigate the role of miRNAs in acquired BRAF inhibitor and imatinib resistance.
Dicer regulation and function in human cancers
Dicer, a ribonuclease enzyme, plays an important role in human miRNA processing. Deregulation of this enzyme can alter miRNA biogenesis and promote tumorigenesis. Although DICER1 mutations have been observed in a small proportion of tumors, the mechanisms of its deregulation in the majority of tumors and how its deregulation can contribute to multiple tumor types remain unclear. The overall aim of this project is to elucidate the mechanism of Dicer regulation and the functional roles of Dicer isoforms in cancer.