Roles of microRNA96 in TGF-beta-Mediated Tumor Progression(2/3)

In Taiwan, cancer has been ranked first place in the top ten causes of death since 1982. The mortality rate and the incidence are rising year by year; therefore, there have been demands for novel diagnosis, prevention, and treatment-related research. We have identified a novel transforming growth factor P (TGFP) signaling pathway that regulates one microRNA (miR96) through Smad-dependent transcriptional regulation. The TGFP-Smad-miR96 signaling is important in promoting metastatic prostate cancer and we have demonstrated that miR96 is involved in regulation of oncogenic/and metastatic progression through mTOR functions. We have characterized the molecular mechanism showing that miR96 can lead to downregulation of the negative regulators of mTOR kinase. Our preliminary findings suggest that this novel TGFP-Smad-miR96 signaling could crosstalk with androgen receptor signaling. Therefore, the TGFP-Smad-miR96 signaling could have important biological effects in metastatic castration-resistant prostate cancer after androgen depletion therapy. Furthermore, the novel TGFP-miR96 signaling is recapitulated in hepatic stellate cells, which is the key extracellular matrix secreting cell in response to TGFP and liver injury. Therefore, miR96 could play an essential role in TGFP-promoted, fibrosis-hepatocellular carcinoma progression. Since miR96 has the potential to be developed into an anti-cancer target or a therapeutic marker, we would like to know its role in cancer biology. We believe that successful execution of our proposed experiments will advance the field in cancer biology and strategy in anti-cancer therapy.