Turra Letícia Passi, Rodrigues Andressa Romualdo, Neto Fermino Sanches Lizarte, Novais Paulo Cezar, Nunes Maria Julia, Tirapelli Victor Cunha, Peria Fernanda Maris, Carneiro Vinícius Marques, de Assis Cirino Mucio Luiz, Carlotti Carlos Gilberto, Tirapelli Daniela Pretti da Cunha
Ribeirão Preto Medical School, University of São Paulo, Department of Surgery and Anatomy Ribeirão Preto - São Paulo, Brazil.
Postgraduate Program in Structural and Functional Interations in Rehabilitation, University of Marília, Marília - São Paulo, Brazil.
Rep Pract Oncol Radiother. 2022 May 19;27(2):215-225. doi: 10.5603/RPOR.a2022.0040. eCollection 2022.
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.
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.
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%).
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.
胶质母细胞瘤是一种无法治愈的肿瘤。其与癌症干细胞（CSCs）相关的缺氧机制表现为缺氧诱导因子1α（HIF-1α）表达调控，这与肿瘤恶性程度直接相关。本研究的目的是在原发性培养中经离子照射的胶质母细胞瘤患者肿瘤干细胞亚群中，确定一种与微小RNA miR-21和miR-326对HIF-1α调控相关的可能的肿瘤恶性特征。
我们使用了10例胶质母细胞瘤患者手术活检的细胞培养物。通过实时聚合酶链反应（PCR）分析微小RNA表达，并将其与死亡率和复发率相关联。ROC曲线显示了各微小RNA相对于临床预后的截断点，并按组进行区分。
miR-21在照射后的神经球组中表达水平较高（p = 0.0028）。然而，miR-21与复发和死亡率无关。miR-326在两组中均与肿瘤复发相关（p = 0.032）；miR-326每增加0.5个单位，复发几率增加1024倍（2.4%）。
照射组中miR-21的高表达表明其在HIF-1α调控和抗辐射神经球中的作用。miR-326增加了两组的复发几率，也表明miR-326的正向调控不依赖于电离辐射治疗。
