Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China.
Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China.
Pathol Res Pract. 2023 Sep;249:154719. doi: 10.1016/j.prp.2023.154719. Epub 2023 Jul 26.
MiR-139-5p is a suppressor in multiple types of cancer. However, whether miR-139-5p affects NSCLC is unknown. In this study, miR-139-5p expression in clinical samples was examined by real-time PCR and in situ hybridization (ISH). MiR-139-5p mimic was transfected to monitor NSCLC cell behaviors. Potential target was predicated using bioinformatics database. Next, whether miR-139-5p impacted cell behaviors via regulation of its predicted target gene were further evaluated. The result revealed that miR-139-5p was lower in NSCLC samples/cells. MiR-139-5p restrained A549 cell proliferation, accelerated apoptosis, and inhibited the β-catenin signaling. ATAD2 was a predicted target of miR-139-5p, and it was highly expressed in NSCLC tissues. ATAD2 overexpression abolished the miR-139-5p's anti-tumor effect on cell proliferation and apoptosis. TWS119 (a β-catenin signaling activator) partially reversed miR-139-5p overexpression-induced suppression of cell proliferation and promotion of cell apoptosis. In tumor xenografts, miR-139-5p restrained tumor growth. MiR-139-5p was a tumor suppressor in NSCLC by regulating the oncogene ATAD2 and β-catenin signaling. Our study provides a promising target for cancer treatment.
miR-139-5p 是多种癌症的抑制因子。然而,miR-139-5p 是否影响 NSCLC 尚不清楚。在本研究中,通过实时 PCR 和原位杂交(ISH)检测临床样本中的 miR-139-5p 表达。转染 miR-139-5p 模拟物以监测 NSCLC 细胞行为。使用生物信息学数据库预测潜在靶标。接下来,进一步评估 miR-139-5p 是否通过调节其预测靶基因来影响细胞行为。结果表明,miR-139-5p 在 NSCLC 样本/细胞中表达降低。miR-139-5p 抑制 A549 细胞增殖,加速细胞凋亡,并抑制 β-catenin 信号。ATAD2 是 miR-139-5p 的预测靶标,在 NSCLC 组织中高表达。ATAD2 过表达消除了 miR-139-5p 对细胞增殖和凋亡的抗肿瘤作用。TWS119(β-catenin 信号激活剂)部分逆转了 miR-139-5p 过表达诱导的细胞增殖抑制和细胞凋亡促进。在肿瘤异种移植中,miR-139-5p 抑制肿瘤生长。miR-139-5p 通过调节癌基因 ATAD2 和 β-catenin 信号在 NSCLC 中起肿瘤抑制作用。我们的研究为癌症治疗提供了一个有前途的靶点。