Department of Burns, the First People's Hospital of Zhengzhou, Zhengzhou, P.R. China.
Henan Institute of Medical and Pharmaceutical Sciences & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, P.R. China.
Anticancer Res. 2023 Nov;43(11):4923-4935. doi: 10.21873/anticanres.16690.
MicroRNAs (miRNAs) are emerging as potential blood-based biomarkers involved in various types of carcinogenesis, including lung adenocarcinoma (LUAD).
In the present study, microarray was used to screen 2,549 miRNAs in serum samples from seven patients with LUAD and seven from healthy controls. Quantitative real-time polymerase chain reaction was used to validate the expression of miRNA in serum samples from 30 patients with LUAD and 30 heathy individuals. The area under the receiver operating characteristic curve was determined to evaluate the diagnostic capability of miR-625-3p. Cell counting kit-8 assay and Transwell assays were used to explore cell proliferation, migration and invasion. Bioinformatics prediction was applied in the search for the target genes of miR-625-3p. Quantitative real-time polymerase chain reaction, western blot and dual luciferase assay were used to validate target genes of miR-625-3p. A xenograft tumor model was established to evaluate cell proliferation in vivo.
miR-625-3p was the miRNA most highly expressed in serum samples from patients with LUAD according to microarray analysis, this finding was verified in sera from an independent cohort, as well as in tissues based on The Cancer Genome Atlas database. Serum miR-625-3p provided a high diagnostic accuracy for LUAD (area under the curve=0.790, 95% confidence interval=0.6640-0.9152). Functionally, miR-625-3p promoted LUAD cell proliferation, migration and invasion both in vivo and in vitro. Mechanistically, we found miR-625-3p promoted cell proliferation and metastasis of LUAD by directly targeting KLF transcription factor 9 (Kruppel-like factor 9, KLF9).
Our study identified that miR-625-3p plays an oncogenic role in LUAD, targeting KLF9. miR-625-3p might be a potential novel diagnostic biomarker and target for LUAD therapy.
MicroRNAs (miRNAs) 作为参与多种类型肿瘤发生的潜在血液生物标志物而备受关注,包括肺腺癌 (LUAD)。
本研究使用微阵列技术筛选了 7 例 LUAD 患者和 7 例健康对照者血清样本中的 2549 个 miRNA。采用实时定量聚合酶链反应验证了 30 例 LUAD 患者和 30 例健康个体血清样本中 miRNA 的表达情况。采用受试者工作特征曲线下面积评估 miR-625-3p 的诊断能力。通过细胞计数试剂盒-8 检测和 Transwell 检测探讨细胞增殖、迁移和侵袭情况。应用生物信息学预测寻找 miR-625-3p 的靶基因。采用实时定量聚合酶链反应、Western blot 和双荧光素酶报告基因检测验证 miR-625-3p 的靶基因。建立异种移植肿瘤模型评估体内细胞增殖情况。
根据微阵列分析,miR-625-3p 是 LUAD 患者血清中表达最高的 miRNA,这一发现通过独立队列的血清样本和基于癌症基因组图谱数据库的组织样本得到了验证。血清 miR-625-3p 对 LUAD 具有较高的诊断准确性(曲线下面积=0.790,95%置信区间=0.6640-0.9152)。功能上,miR-625-3p 在体内和体外均促进 LUAD 细胞的增殖、迁移和侵袭。机制上,我们发现 miR-625-3p 通过直接靶向 Kruppel 样因子 9 (KLF9) 促进 LUAD 细胞的增殖和转移。
本研究发现 miR-625-3p 在 LUAD 中发挥致癌作用,靶向 KLF9。miR-625-3p 可能成为 LUAD 潜在的新型诊断生物标志物和治疗靶点。