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

Abstract

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.

• Authors: 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
• Journal: Oral oncology (Oral Oncol) Vol. 47 Issue 3 Pg. 202-10 (Mar 2011) ISSN: 1879-0593 [Electronic] England
• PMID: 21292542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Homeodomain Proteins
• MicroRNAs
• NANOG protein, human
• Nanog Homeobox Protein
• Octamer Transcription Factor-3
• mirnlet7 microRNA, human

Topics

• Animals
• Carcinoma, Squamous Cell (genetics, metabolism, secondary)
• Cohort Studies
• Female
• Gene Expression Regulation, Neoplastic
• Genes, Tumor Suppressor
• Head and Neck Neoplasms (genetics, metabolism, pathology)
• Homeodomain Proteins (metabolism)
• Humans
• Lymphatic Metastasis
• Male
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Nanog Homeobox Protein
• Octamer Transcription Factor-3 (metabolism)
• Taiwan