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

Research output: Contribution to journalArticle

88 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)202-210
Number of pages9
JournalOral Oncology
Volume47
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

Fingerprint

Head and Neck Neoplasms
MicroRNAs
Neoplastic Stem Cells
Neoplasms

Keywords

  • Chemoresistance
  • Let-7a
  • Metastasis
  • MicroRNA
  • Nanog
  • Oct4
  • Tumour initiating cells

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

Cite this

MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation. / Yu, Cheng Chia; Chen, Yi Wei; Chiou, Guang Yuh; Tsai, Lo Lin; Huang, Pin I.; Chang, Charn Yung; Tseng, Ling Ming; Chiou, Shih Hwa; Yen, Sang Hue; Chou, Ming Yung; Chu, Pen Yuan; Lo, Wen Liang.

In: Oral Oncology, Vol. 47, No. 3, 03.2011, p. 202-210.

Research output: Contribution to journalArticle

Yu, CC, Chen, YW, Chiou, GY, Tsai, LL, Huang, PI, Chang, CY, Tseng, LM, Chiou, SH, Yen, SH, Chou, MY, Chu, PY & Lo, WL 2011, 'MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation', Oral Oncology, vol. 47, no. 3, pp. 202-210. https://doi.org/10.1016/j.oraloncology.2010.12.001
Yu, Cheng Chia ; Chen, Yi Wei ; Chiou, Guang Yuh ; Tsai, Lo Lin ; Huang, Pin I. ; Chang, Charn Yung ; Tseng, Ling Ming ; Chiou, Shih Hwa ; Yen, Sang Hue ; Chou, Ming Yung ; Chu, Pen Yuan ; Lo, Wen Liang. / MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation. In: Oral Oncology. 2011 ; Vol. 47, No. 3. pp. 202-210.
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AU - Huang, Pin I.

AU - Chang, Charn Yung

AU - Tseng, Ling Ming

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AU - Chou, Ming Yung

AU - Chu, Pen Yuan

AU - Lo, Wen Liang

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