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

Lee D, Sun S, Zhang XQ, Zhang PD, Ho AS, Kiang KM, Fung CF, Lui WM, Leung GK - J Cancer (2015)

Bottom Line: 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.The findings have important translational implications in suggesting new directions of future studies.

View Article: PubMed Central - PubMed

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

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

MiR-210 regulates P4HB expression. (A) Transfection of miR-210 mimics successfully results in miR-210 overexpressions in all four GBM cell lines when compared with their respective negative controls on qPCR. (B) Downregulation in the relative P4HB expression levels occurs as the result of miR-210 overexpressions when compared to their respective negative controls. (** = p < 0.01; *** = p < 0.001)
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Figure 3: MiR-210 regulates P4HB expression. (A) Transfection of miR-210 mimics successfully results in miR-210 overexpressions in all four GBM cell lines when compared with their respective negative controls on qPCR. (B) Downregulation in the relative P4HB expression levels occurs as the result of miR-210 overexpressions when compared to their respective negative controls. (** = p < 0.01; *** = p < 0.001)

Mentions: We then overexpressed miR-210 to evaluate its potential regulatory action on P4HB. The transfection efficiency of the miR-210 mimic was confirmed by qPCR, which showed an increase in relative fold ratios by 100 times when compared with control (Fig. 3A). Due to the intrinsically higher expression of miR-210 in the TMZ-sensitive cells, the absolute levels of miR-210 expression were higher in the parental D54-S and U87-S cells when compared to their resistant counterparts.


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

Lee D, Sun S, Zhang XQ, Zhang PD, Ho AS, Kiang KM, Fung CF, Lui WM, Leung GK - J Cancer (2015)

MiR-210 regulates P4HB expression. (A) Transfection of miR-210 mimics successfully results in miR-210 overexpressions in all four GBM cell lines when compared with their respective negative controls on qPCR. (B) Downregulation in the relative P4HB expression levels occurs as the result of miR-210 overexpressions when compared to their respective negative controls. (** = p < 0.01; *** = p < 0.001)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4317757&req=5

Figure 3: MiR-210 regulates P4HB expression. (A) Transfection of miR-210 mimics successfully results in miR-210 overexpressions in all four GBM cell lines when compared with their respective negative controls on qPCR. (B) Downregulation in the relative P4HB expression levels occurs as the result of miR-210 overexpressions when compared to their respective negative controls. (** = p < 0.01; *** = p < 0.001)
Mentions: We then overexpressed miR-210 to evaluate its potential regulatory action on P4HB. The transfection efficiency of the miR-210 mimic was confirmed by qPCR, which showed an increase in relative fold ratios by 100 times when compared with control (Fig. 3A). Due to the intrinsically higher expression of miR-210 in the TMZ-sensitive cells, the absolute levels of miR-210 expression were higher in the parental D54-S and U87-S cells when compared to their resistant counterparts.

Bottom Line: 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.The findings have important translational implications in suggesting new directions of future studies.

View Article: PubMed Central - PubMed

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

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus