miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells

研究焦點

論文名稱

英文:miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells

作者:核醫科 翁瑞鴻 主治醫師

本篇論文發表於 International Journal of Molecular Sciences 期刊  Int. J. Mol. Sci. 2016, 17, 1092 全文下載

研究目的:

本研究計畫中,我們計畫利用已建立的人類癌細胞株,以小球(phere)培養方式獲得癌幹細胞後,進行扁柏醇抑制癌幹細胞特性之分子機制探討。

研究結果:

a.了解扁柏醇是具有抑制幹細胞之自我更新(self-renewal)的活性

b.扁柏醇抑制癌幹細胞的分子機制,包含透過誘導特定微小RNA的表現

miR-494-3p could enhance the radiosensitivity of SAS OSCC cells and induce cellular senescence. The overexpression of miR-494-3p in SAS cells increased the population of senescence-associated-galactosidase positive cells, the expression of p16INK4a and retinoblastoma 1 (RB1), as well as downregulated Bmi1. The knockdown of Bmi1 by lentiviral-mediated delivery of specific short hairpin RNAs (shRNAs) also enhanced the radiosensitivity of SAS cells and the activation of the senescence pathway. Furthermore, the inverse correlation between Bmi1 and miR-494-3p expression was observed among OSCC tissues.

研究貢獻與臨床應用:

透過研究證實 miR-494-3p 能增加扁平細胞癌對放射治療的敏感性,且機制為透過調控下游Bmi1.

有上述的研究成果,下一步則是大量收集臨床口腔癌病人檢體,確認機制存在的比例,進一步研發同功效小分子結構物,以作為癌症新藥的開發。