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; Andressa Romualdo Rodrigues; Fermino Sanches Lizarte Neto; Paulo Cezar Novais; Maria Julia Nunes; Victor Cunha Tirapelli; Fernanda Maris Peria; Vinícius Marques Carneiro; Mucio Luiz de Assis Cirino; Carlos Gilberto Carlotti Jr; Daniela Pretti da Cunha Tirapelli

doi:10.5603/RPOR.a2022.0040

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

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

Affiliations

¹ Ribeirão Preto Medical School, University of São Paulo, Department of Surgery and Anatomy Ribeirão Preto - São Paulo, Brazil.
² Postgraduate Program in Structural and Functional Interations in Rehabilitation, University of Marília, Marília - São Paulo, Brazil.
³ Anhanguera College of Ribeirão Preto, Ribeirão Preto - São Paulo, Brazil.

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.