MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation

Cheng Chia Yu, Yi Wei Chen, Guang Yuh Chiou, Lo Lin Tsai, Pin I. Huang, Charn Yung Chang, Ling Ming Tseng, Shih Hwa Chiou, Sang Hue Yen, Ming Yung Chou, Pen Yuan Chu, Wen Liang Lo

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115 引文 斯高帕斯(Scopus)


Head and neck cancer (HNC) is a prevalent cancer worldwide. Let-7 has been shown to function as a tumour suppressor by regulating multiple oncogenic signalling pathways. However, the role of let-7 in head and neck cancer (HNC) and in HNC-associated tumour initiating cells (TIC) remains unclear. In this study, we first demonstrated that let-7a expression was significantly decreased but that Nanog/Oct4 expression was increased in HNC tissues as compared to adjacent normal cells. Expression of let-7a in recurrent HNC tissue and in regional metastatic lymph nodes of HNC patients was also significantly decreased, but Nanog/Oct4 expression was increased as compared to the expression levels in the parental tumours. Consistently, the stemness genes were significantly up-regulated and let-7a was down-regulated in HNC-ALDH1 + cells relative to HNC-ALDH1- cells. Furthermore, lentiviral-mediated let-7a overexpression could significantly inhibit the stemness signature and the chemoresistant abilities of HNC-ALDH1+ cells. Most importantly, overexpression of let-7 or knockdown of Nanog in ALDH1+ cells effectively blocked tumour metastasis and significantly prolonged survival time in ALDH1+-transplanted immunocompromised mice. Overall, restoration of let-7a in HNC and HNC-TIC may be a new approach for the therapeutic treatment of HNC in the future. These results show that let-7a negatively modulates the expression of stemness genes and plays a role as a tumour suppressor in HNC by eliminating the putative HNC-TIC population.
頁(從 - 到)202-210
期刊Oral Oncology
出版狀態已發佈 - 3月 2011

ASJC Scopus subject areas

  • 腫瘤科
  • 口腔外科
  • 癌症研究


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