Regulation of autophagy by miR-30d impacts sensitivity of anaplastic thyroid carcinoma to cisplatin

Y. Zhang, W. Q. Yang, H. Zhu, Y. Y. Qian, L. Zhou, Y. J. Ren, X. C. Ren, L. Zhang, X. P. Liu, C. G. Liu, Z. J. Ming, B. Li, B. Chen, J. R. Wang, Y. B. Liu, J. M. Yang

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

miR-30d has been observed to be significantly down-regulated in human anaplastic thyroid carcinoma (ATC), and is believed to be an important event in thyroid cell transformation. In this study, we found that miR-30d has a critical role in modulating sensitivity of ATC cells to cisplatin, a commonly used chemotherapeutic drug for treatment of this neoplasm. Using a mimic of miR-30d, we demonstrated that miR-30d could negatively regulate the expression of beclin 1, a key autophagy gene, leading to suppression of the cisplatin-activated autophagic response that protects ATC cells from apoptosis. A reporter gene assay demonstrated that the binding sequences of miR-30d in the beclin 1-3′ UTR was the region required for the inhibition of beclin 1 expression by this miRNA. We further showed that inhibition of the beclin 1-mediated autophagy by the miR-30d mimic sensitized ATC cells to cisplatin both in vitro (cell culture) and in vivo (animal xenograft model). These results suggest that dysregulation of miR-30d in ATC cells is responsible for the insensitivity to cisplatin by promoting autophagic survival. Thus, miR-30d may be exploited as a potential target for therapeutic intervention in the treatment of ATC.

Original languageEnglish (US)
Pages (from-to)562-570
Number of pages9
JournalBiochemical Pharmacology
Volume87
Issue number4
DOIs
StatePublished - Feb 15 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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