Dabiri Arezou, Sharifi Mohammadreza, Sarmadi Akram
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Int J Mol Cell Med. 2021 Fall;10(4):249-258. doi: 10.22088/IJMCM.BUMS.10.4.249. Epub 2022 Jun 6.
Recent improvements in molecular treatment and gene therapy led to discovering novel cancer remedies. Antisense LNA GapmeRs is a state-of-the-art molecular research field for diagnosing and treating various cancer types. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy defined by the rapid accumulation and malignant proliferation of immature myeloid progenitors. SOX12 is a new potential target for acute myeloid leukemia. In this study, SOX12 was blocked by antisense LNA GapmeRs (ALG) in human AML cell lines (KG1 and M07e). Cells were transfected with Gapmer anti- at 24, 48, and 72 h post-transfection. Transfection efficiency was assessed by a fluorescent microscope. Furthermore, evaluation of SOX12, TWIST1, CTNNB1, CASP3, and CASP9 expression was performed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell viability was determined by MTT assay. SOX12 expression was decreased remarkably in the ALG group. Moreover, SOX12 knockdown was associated with a decrease in and expression. Besides, downregulation of SOX12 in both cell lines could induce apoptosis, probably through upregulation of CASP3 and CASP9. The findings reveal that SOX12 knockdown could be a new target for reducing AML cells proliferation through antisense therapy approach.
分子治疗和基因治疗方面的最新进展促使人们发现了新型癌症治疗方法。反义锁核酸GapmeRs是诊断和治疗各种癌症类型的前沿分子研究领域。急性髓系白血病（AML）是一种异质性造血恶性肿瘤，其特征是未成熟髓系祖细胞的快速积累和恶性增殖。SOX12是急性髓系白血病的一个新的潜在靶点。在本研究中，反义锁核酸GapmeRs（ALG）在人AML细胞系（KG1和M07e）中阻断了SOX12。在转染后24、48和72小时用Gapmer反义核酸转染细胞。通过荧光显微镜评估转染效率。此外，通过定量逆转录聚合酶链反应（qRT-PCR）对SOX12、TWIST1、CTNNB1、CASP3和CASP9的表达进行评估。通过MTT法测定细胞活力。ALG组中SOX12的表达显著降低。此外，SOX12的敲低与[此处原文缺失相关内容]和[此处原文缺失相关内容]表达的降低有关。此外，两种细胞系中SOX12的下调可能通过上调CASP3和CASP9诱导细胞凋亡。这些发现表明，通过反义治疗方法敲低SOX12可能是减少AML细胞增殖的一个新靶点。
