Ege University, Faculty of Medicine, Department of Medical Genetics, 35100, Bornova, Izmir, Turkey.
Aydin Adnan Menderes University, Faculty of Medicine, Department of Medical Biology, 09100 Aydin, Turkey.
Biomed Res Int. 2021 Nov 28;2021:3207328. doi: 10.1155/2021/3207328. eCollection 2021.
Prednisolone has been used frequently in the treatment of acute lymphoblastic leukemia. However, to overcome the challenges of the treatment, the development of additional therapies is of great importance. Small, non-protein-coding RNAs, namely, microRNAs (miRNAs), are critical epigenetic regulators with physiological and pathological importance. This study is aimed at determining the effects of miR-146a, miR-155, and miR-181a inhibition with their corresponding anti-miRs on both leukemic and healthy cells, individually and with prednisolone. Leukemic (SUP-B15) and healthy B-lymphocyte (NCI-BL 2171) cell lines were used in this study. A total of 12 experimental groups included individual and combinational silenced ALL-associated miRNAs (hsa-miR-155, hsa-miR-146a, and hsa-miR-181a) and their combination with prednisolone. Cytotoxicity, proliferation, cell cycle, and apoptosis analyses were performed by using WST-1, trypan blue, APC-BrdU, Annexin V, and JC-1 methods in each study group, respectively. To control the effectiveness of anti-miR transfection and prednisolone application, miRNA expression analysis was performed from all groups. Anti-miR application was effective on the viability, proliferation, cell cycle, and apoptosis of leukemia cells, and this effect was increased with prednisolone administration. In addition, this activity was found to be very low on healthy cells. In conclusion, anti-miR applications may have the potential for clinical use of adjuvant to or as an alternative to conventional therapies for childhood acute lymphoblastic leukemia.
泼尼松龙在治疗急性淋巴细胞白血病中经常被使用。然而，为了克服治疗中的挑战，开发额外的治疗方法非常重要。小的、非蛋白编码的 RNA，即 microRNAs (miRNAs)，是具有生理和病理重要性的关键表观遗传调节剂。本研究旨在确定 miR-146a、miR-155 和 miR-181a 的抑制及其对应的反义寡核苷酸对白血病和健康细胞的单独和与泼尼松龙的影响。本研究使用了白血病（SUP-B15）和健康 B 淋巴细胞（NCI-BL 2171）细胞系。共有 12 个实验组，包括单独和组合沉默的 ALL 相关 miRNA（hsa-miR-155、hsa-miR-146a 和 hsa-miR-181a）及其与泼尼松龙的组合。通过 WST-1、台盼蓝、APC-BrdU、Annexin V 和 JC-1 方法分别在每个研究组中进行细胞毒性、增殖、细胞周期和凋亡分析。为了控制反义寡核苷酸转染和泼尼松龙应用的有效性，对所有组进行了 miRNA 表达分析。反义寡核苷酸的应用对白血病细胞的活力、增殖、细胞周期和凋亡有效，并且这种作用随着泼尼松龙的给药而增加。此外，这种活性在健康细胞中非常低。总之，反义寡核苷酸的应用可能具有作为儿童急性淋巴细胞白血病的辅助治疗或替代常规治疗的临床应用潜力。
