Let-7c restores radiosensitivity and chemosensitivity and impairs stemness in oral cancer cells through inhibiting interleukin-8

Chih Yu Peng, Tung Yuan Wang, Shiuan Shinn Lee, Pei Ling Hsieh, Yi Wen Liao, Lo Lin Tsai, Chih Yuan Fang, Cheng Chia Yu, Ching Shui Hsieh

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: The let-7 family of microRNAs has been considered as tumor suppressors in various cancers; however, the role of let-7c in oral squamous cell carcinoma has not been determined yet. Methods: In this study, phenotypical behaviors and the radio/chemoresistance were examined subsequent to overexpression of let-7c. In addition, the expression of let-7c in cancer stem cells (CSCs) was evaluated and the effect of let-7c on stemness characteristics was assessed. Also, luciferase activity assays were performed to test whether interleukin (IL)-8 was a putative target of let-7c. Results: Our results confirmed that the expression of let-7c in CSCs was reduced, while overexpression of let-7c attenuated the oncogenicity. Moreover, ectopic expression of let-7c in CSCs downregulated the stemness hallmarks and the radio/chemoresistance. Expression and secretion of IL-8 in oral CSCs were both reduced following overexpression of let-7c. Besides, the inhibitory effect of let-7c on various stemness phenotypes was reverted by IL-8, indicating that lower expression of let-7c may confer higher cancer stemness through a failure to downregulate IL-8. Conclusion: These findings revealed the significance of let-7c in the contribution of oral cancer stemness and radio/chemoresistance. Targeting let-7c and its downstream IL-8 may be beneficial to prevent cancer recurrence and metastasis of oral squamous cell carcinoma.

Original languageEnglish
JournalJournal of Oral Pathology and Medicine
DOIs
Publication statusAccepted/In press - Jan 1 2018

Keywords

  • Cancer stemness
  • Interleukin-8
  • Let-7c
  • Oral squamous cell carcinomas
  • Radio/chemoresistance

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oral Surgery
  • Otorhinolaryngology
  • Cancer Research
  • Periodontics

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