J Cancer 2015; 6(3):227-232. doi:10.7150/jca.10765

Short Research Communication

MicroRNA-210 and Endoplasmic Reticulum Chaperones in the Regulation of Chemoresistance in Glioblastoma

Derek Lee, Stella Sun, Xiao Qin Zhang, Ping De Zhang, Amy S.W. Ho, Karrie M.Y. Kiang, Ching Fai Fung, Wai Man Lui, Gilberto K.K. Leung

Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong

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Lee D, Sun S, Zhang XQ, Zhang PD, Ho ASW, Kiang KMY, Fung CF, Lui WM, Leung GKK. MicroRNA-210 and Endoplasmic Reticulum Chaperones in the Regulation of Chemoresistance in Glioblastoma. J Cancer 2015; 6(3):227-232. doi:10.7150/jca.10765. Available from http://www.jcancer.org/v06p0227.htm

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Glioblastoma multiforme (GBM) is the commonest primary brain tumour in adults characterized by relentless recurrence due to resistance towards the standard chemotherapeutic agent temozolomide (TMZ). Prolyl 4-hydroxylase, beta polypeptide (P4HB), an endoplasmic reticulum (ER) chaperone, is known to be upregulated in TMZ-resistant GBM cells. MicroRNAs (miRNAs) are non-protein-coding transcripts that may play important roles in GBM chemoresistance. We surmised that miRNA dysregulations may contribute to P4HB upregulation, hence chemoresistance. We found that miRNA-210 (miR-210) was P4HB-targeting and was highly downregulated in TMZ-resistant GBM cells. Forced overexpression of miR-210 led to P4HB downregulation and a reduction in TMZ-resistance. A reciprocal relationship between their expressions was also verified in clinical glioma specimens. Our study is the first to demonstrate a potential link between miR-210 and ER chaperone in determining chemosensitivity in GBM. The findings have important translational implications in suggesting new directions of future studies.

Keywords: Glioblastoma, miRNA, P4HB, ER stress reponse, chemoresistance, temozolomide