The role of miR-455-5p in the tumorigenesis of oral cancer

  • 鄭 昭旻

學生論文: Doctoral Thesis

摘要

Oral cancer ranks the fourth common cause of cancer death for men in Taiwan and the incidence is increasing year by year The standard treatment for patients in late stage is concurrent chemoradiotherapy The major causes of death in oral cancer patients are local recurrence at the primary site and distant metastasis In addition despite advancement in the treatment the 5-year survival and overall survival rate are still lower than 50% Therefore understanding the underlying detailed mechanism/s of oral cancer is urgent to help to design novel therapeutic strategy We have identified previously that the expression level of miR-455-5p is higher in tumor tissues and oral cancer cell lines than that in normal tissues and normal cell line respectively Inhibition of miR-455-5p decreased the anchorage-independent growth and proliferative abilities through regulating cell cycle check point proteins suggesting miR-455-5p is an oncomiR in oral cancer tumorigenesis By combining the array data from cancer patients and cell lines and intersecting with the prediction results from websites to filter out possible candidates ubiquitin conjugating enzyme 2B (UBE2B) was identified The 3’-UTR luciferase reporter assay and western blot analysis further confirmed that UBE2B is a target gene of miR-455-5p In soft agar colony formation assay UBE2B suppression rescued the cell transformation ability that decreased by miR-455-5p knockdown Microenvironmental changes and tumor hypoxia may increase the secretion of cytokines including transforming growth factor-β (TGF-β) which has been reported to play a crucial role in premalignant and metastasis stage of oral cancer and the link between these factors and miR-455-5p is still unclear Our data demonstrated that TGF-β regulates miR-455-5p and UBE2B expression through the binding of Smad3 on the promoter regions These results were further validated in animal experiments Importantly miR-455-5p expression was associated with the nodal status stage and overall survival in our patients suggesting that miR-455-5p is a potential marker for predicting the prognosis of patients with oral cancer In conclusion we reveal that miR-455-5p expression is regulated by the TGF-β-dependent pathway which subsequently leads to UBE2B down-regulation and contributes to oral cancer tumourigenesis
獎項日期2016 八月 2
原文English
監督員Jang-Yang Chang (Supervisor)

引用此文

The role of miR-455-5p in the tumorigenesis of oral cancer
昭旻, 鄭. (Author). 2016 八月 2

學生論文: Doctoral Thesis