Our primary research interests focus on erbB receptor tyrosine kinases (RTKs)-mediated signal transduction in breast cancer and noncoding RNA (ncRNA)-mediated epigenetic regulation of drug resistance and metastasis. By understanding the molecular basis of RTK signaling in tumorigenesis and ncRNA, including miRNA and lncRNA, regulation of tumor progression, we hope to identify novel targets and develop epigenetic approaches with therapeutic potential for cancer treatment.
There are currently three areas of investigation in my laboratory:
Project 1: Role of erbB3 signaling in cancer drug resistance and tumor metastasis. Our recent data show that the erbB3 signaling exerts its biologic function via regulation of two tumor suppressive miRNAs, miR-203 and miR-542-3p. Modern molecular and cellular biology techniques are applied to determine how miR-203 and miR-542-3p contribute to erbB3-mediated drug resistance and tumor metastasis.
Project 2: Identification of novel erbB3-targeted therapy. Our ongoing studies aim to determine whether the novel strategy/agents targeting of erbB3 (cooperative miRNAs and epigenetic modulators) may abrogate or attenuate the therapeutic resistance to tamoxifen, paclitaxel, and/or trastuzumab against erbB2-overexpressing (erbB2+) breast cancer.
Project 3: Epigenetic enhancement of chemotherapy against non-small cell lung cancer (NSCLC), multiple myeloma (MM), acute myeloid leukemia (AML). We have discovered that the HDAC inhibitors, such as entinostat, panobinostat, and SAHA are able to induce expression of tumor suppressive miRNAs and lncRNAs, leading to downregulation of Survivin and several key EMT markers, respectively. Our studies suggest that ncRNA-mediated epigenetic approach is a useful strategy to significantly potentiate chemotherapeutic agents-induced antitumor activity.
1. Huang, J., Lyu, H., Wang, J., and Liu, B. MicroRNA regulation and therapeutic targeting of Survivin in cancer. American Journal of Cancer Research 2015; 5(1):20-31.
2. Huang, J., Lyu, H., Wang, J., and Liu, B. Influence of survivin-targeted therapy on chemosensitivity in the treatment of acute myeloid leukemia. Cancer Letters 2015; 366: 160-172.
3. Lyu, H., Huang, J., Edgerton, S.M., Thor, A.D., He, Z., and Liu, B. Increased erbB3 promotes erbB2/neu-driven mammary tumor proliferation and co-targeting of erbB2/erbB3 receptors exhibits potent inhibitory effects on breast cancer cells. International Journal of Clinical and Experimental Pathology 2015; 8(6):6143-6156.
4. Lyu, H., Yang, X., Edgerton, S.M., Thor, A.D., Wu, X., He, Z., and Liu, B. The erbB3- and IGF-1 receptor-initiated signaling pathways exhibit distinct effects on lapatinib sensitivity against trastuzumab-resistant breast cancer cells. Oncotarget 2016;7(3): 2921-2935.
5. Wang, S., Zhu, L., Zuo, W., Zeng, Z., Huang, L., Lin, L., Lin, R., Wang, J., Lu, J., Wang, Q., Lin, L., Dong, H., Wu, W., Zheng, K., Cai, J., Yang, S., Ma, Y., Ye, S., Liu, W., Yu, Y., Tan, J., and Liu, B. MicroRNA-mediated epigenetic targeting of Survivin significantly enhances the antitumor activity of paclitaxel against non-small cell lung cancer. Oncotarget 2016;7(25): 37693-37713.
6. Wu, Y., Lyu, H., Liu, H., Shi, X., Song, Y., and Liu, B. Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer. Scientific Reports 2016; 6: 31093.