Non-coding RNAs provide new opportunities to identify biomarkers that properly classify cancer patients. Here, we study the biomarker status of the mitochondrial long non-coding RNAs, MDL1 and MDL1AS. Expression of these genes was studied in public transcriptomic databases. In addition, a cohort of 69 locally advanced rectal cancer (LARC) patients with a follow-up of more than 5 years was used to determine the prognostic value of these markers. Furthermore, cell lines of colorectal (HCT116) and breast (MDA-MB-231) carcinoma were employed to study the effects of downregulating MDL1AS in vitro. Expression of MDL1AS (but not MDL1) was significantly different in tumor cells than in the surrounding tissue in a tumor-type-specific context. Both MDL1 and MDL1AS were accurate biomarkers for the 5-year survival of LARC patients (p= 0.040 andp= 0.007, respectively) with promising areas under the curve in the ROC analyses (0.820 and 0.930, respectively). MDL1AS downregulation reduced mitochondrial respiration in both cell lines. Furthermore, this downregulation produced a decrease in growth and migration on colorectal cells, but the reverse effects on breast cancer cells. In summary, MDL1 and MDL1AS can be used as reliable prognostic biomarkers of LARC, and MDL1AS expression provides relevant information on the diagnosis of different cancers.
非编码RNA为准确分类癌症患者的生物标志物鉴定提供了新机遇。本研究聚焦于线粒体长链非编码RNA——MDL1及其反义转录本MDL1AS的生物标志物价值。通过分析公共转录组数据库，我们系统研究了这些基因的表达特征。同时，基于69例随访超过5年的局部晚期直肠癌患者队列，评估了这些标志物的预后价值。此外，研究采用结直肠癌（HCT116）和乳腺癌（MDA-MB-231）细胞系，在体外探讨了敲低MDL1AS的生物学效应。 研究发现，在肿瘤类型特异性背景下，MDL1AS（而非MDL1）在肿瘤细胞与癌旁组织中的表达存在显著差异。在局部晚期直肠癌患者5年生存期预测中，MDL1与MDL1AS均展现出良好的生物标志物效能（p值分别为0.040和0.007），受试者工作特征曲线下面积分别达到0.820和0.930。体外实验表明，敲低MDL1AS可降低两种细胞系的线粒体呼吸功能。值得注意的是，该干预在结直肠癌细胞中抑制了增殖与迁移能力，但在乳腺癌细胞中却产生相反效应。 综上所述，MDL1与MDL1AS可作为局部晚期直肠癌可靠的预后生物标志物，而MDL1AS的表达水平对不同癌症的诊断具有重要参考价值。
肿瘤(癌症)患者之家