Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Biochemical pharmacology, 2014-02, Vol.87 (4), p.562-570

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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.