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. 2022 May 19;27(2):215-225.
doi: 10.5603/RPOR.a2022.0040. eCollection 2022.

Expression of microRNAs miR-21 and miR-326 associated with HIF-1α regulation in neurospheres of glioblastoma submitted to ionizing radiation treatment

Letícia Passi Turra  1 , Andressa Romualdo Rodrigues  1 , Fermino Sanches Lizarte Neto  1 , Paulo Cezar Novais  1   2 , Maria Julia Nunes  1 , Victor Cunha Tirapelli  1 , Fernanda Maris Peria  1 , Vinícius Marques Carneiro  1 , Mucio Luiz de Assis Cirino  1   3 , Carlos Gilberto Carlotti Jr  1 , Daniela Pretti da Cunha Tirapelli  1
Affiliations

Expression of microRNAs miR-21 and miR-326 associated with HIF-1α regulation in neurospheres of glioblastoma submitted to ionizing radiation treatment

Letícia Passi Turra et al. Rep Pract Oncol Radiother. .

Abstract

Background: Glioblastoma is an incurable neoplasm. Its hypoxia mechanism associated with cancer stem cells (CSCs) demonstrates hypoxia-inducible factor 1α (HIF-1α) expression regulation, which is directly related to tumor malignancy. The aim of this study was to identify a possible tumor malignancy signature associated with regulation of HIF-1α by microRNAs miR-21 and miR-326 in the subpopulation of tumor stem cells which were irradiated by ion in primary culture of patients diagnosed with glioblastoma.

Materials and methods: We used cellular cultures from surgery biopsies of ten patients with glioblastoma. MicroRNA expressions were analyzed through real-time polymerase chain reaction (PCR ) and correlated with mortality and recurrence. The ROC curve displayed the cutoff point of the respective microRNAs in relation to the clinical prognosis, separating them by group.

Results: The miR-21 addressed high level of expression in the irradiated neurosphere group (p = 0.0028). However, miR-21 was not associated with recurrence and mortality. miR-326 can be associated with tumoral recurrence (p = 0.032) in both groups; every 0.5 units of miR-326 increased the chances of recurrence by 1,024 (2.4%).

Conclusion: The high expression of miR-21 in the irradiated group suggests its role in the regulation of HIF-1α and in the radioresistant neurospheres. miR-326 increased the chances of recurrence in both groups, also demonstrating that positive regulation from miR-326 does not depend on ionizing radiation treatment.

Keywords: glioblastoma; ionizing radiation; microRNAs.

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Conflict of interest statement

Conflict of interest The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
A. Representation of miR-326 expression in neurospheres treated with ionizing radiation. It can be observed that there was no statistical difference (p = 0.6309); B. Representation of miR-21 expression in neurospheres treated with ionizing radiation. It can be noticed that there was a significant increase in the irradiated neurospheres (R) in comparison to the control group (C) (p = 0.0028)
Figure 2
Figure 2
AB. Representation of the median regarding the recurrence for microRNAs miR-21 and miR-326 expressed in neurospheres relative to the groups studied; CD. Representation of the median regarding mortality of microRNAs miR-21 and miR-326 expressed relative to neurospheres in the groups studied
Figure 3
Figure 3
AB. Representation of the median regarding the recurrence of microRNAs miR-21 and miR-326 expressed relative to the neurospheres; CD. Representation of the median regarding mortality of microRNAs miR-21 and miR-326
Figure 4
Figure 4
AB. ROC curves of miR-21 as a predictive value for recurrence and mortality relative to the neurosphere control group; CD. ROC curves of miR-21 as a predictive value for recurrence and mortality related to the irradiated neurosphere
Figure 5
Figure 5
AB. ROC curves of miR-326 as a predictive value of recurrence and mortality relative to the neurosphere control group; CD. ROC curves of miR-326 as a predictive value of recurrence relative to the irradiated neurosphere group
See this image and copyright information in PMC

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