Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Sci Rep. 2023 Jul 31;13(1):12371. doi: 10.1038/s41598-023-39000-0.
The oncogenic role of long non-coding RNA SOX2 overlapping transcript (SOX2-OT) has been demonstrated as a miRNA decay system that sponges tumor suppressor miRNA, including miR-122-3p in glioblastoma and miR-194-5p in glioblastoma, gastric, and colorectal cancers. However, the molecular function of SOX2-OT remains unknown in most cancers, including lung cancer. In the current study, we aimed to evaluate the downstream regulatory function of SOX2-OT in A549 and Calu-3 lung cancer cell lines. We knocked down SOX2-OT expression using an RNA interference system, which significantly decreased expression in A549 and Calu-3 cells. The expression of down-regulating miRNAs (miR-122-3p and miR-194-5p) was evaluated, revealing increased expression of miR-122-3p and miR-194-5p. Additionally, the expression of miRNAs downstream mRNA, including FOXO1 (Forkhead Box O1) and FOXA1 (Forkhead Box O1), changed. Recently, critical roles of FOXO1 and FOXA1 proteins in pathways involved in proliferation, metastasis and apoptosis have been demonstrated. Downstream changes in cellular traits were assessed using MTT, flow cytometry, metastasis and apoptosis assays. These assessments confirmed that the biological behaviors of lung cancer cells were influenced after SOX2-OT knockdown. In summary, the present study highlights the oncogenic role of SOX2-OT through the regulation of miR-122-3p/FOXO1 and miR-194-5p/FOXA1 pathways.
长链非编码 RNA SOX2 重叠转录物(SOX2-OT)的致癌作用已被证明是一种 miRNA 降解系统,可吸收肿瘤抑制 miRNA,包括脑胶质瘤中的 miR-122-3p 和脑胶质瘤、胃癌和结直肠癌中的 miR-194-5p。然而,SOX2-OT 的分子功能在大多数癌症中仍然未知,包括肺癌。在本研究中,我们旨在评估 SOX2-OT 在 A549 和 Calu-3 肺癌细胞系中的下游调节功能。我们使用 RNA 干扰系统敲低 SOX2-OT 表达,这显著降低了 A549 和 Calu-3 细胞中的表达。评估下调 miRNA(miR-122-3p 和 miR-194-5p)的表达,发现 miR-122-3p 和 miR-194-5p 的表达增加。此外,下游 mRNA 的 miRNA 表达,包括 FOXO1(叉头框 O1)和 FOXA1(叉头框 O1),发生变化。最近,FOXO1 和 FOXA1 蛋白在增殖、转移和凋亡相关途径中的关键作用已得到证实。使用 MTT、流式细胞术、转移和凋亡测定评估细胞特性的下游变化。这些评估证实,SOX2-OT 敲低后会影响肺癌细胞的生物学行为。总之,本研究通过调节 miR-122-3p/FOXO1 和 miR-194-5p/FOXA1 途径强调了 SOX2-OT 的致癌作用。