Department of Genetics and Biotechnology, School of Biological Science, Varamin Pishva Branch, Islamic Azad University, Varamin, Iran.
Molecular Medicine Department, Biotechnology Research center, Pasteur Institute of Iran, Tehran, Iran.
Asian Pac J Cancer Prev. 2021 Mar 1;22(3):947-955. doi: 10.31557/APJCP.2021.22.3.947.
Recent studies have shown the role of autophagy in different types of cancer including lung cancer. MicroRNAs are considered as key factors in regulation of autophagy related genes. miR-30d, miR-204-5p and miR-20a are regulatory markers which can suppress the expression of beclin1, LC3, bcl2 and ULK1 as their target genes and they lead to decrement of autophagy in human cancer cells. Moreover, epigenetic modifications DNA methylation has been indicated in regulation of autophagy in different stages of cancer.
In this study, the expression levels of miR-30d, miR-204-5p and miR-20a as well as their target genes were analyzed in 30 non-small cell lung cancers (NSCLCs) patients sample and adjacent normal tissues by real-time qPCR. In addition, DNA methylation of beclin1, LC3, bcl2 and ULK1 genes were assessed by MS-HRM method.
MiR-30d (p value= 0.01) and miR-204-5p (P=0.048) significantly down-regulated in tumor samples compared to normal adjacent tissues, while there was no significant change in expression level of miR-20a. On the other hand, target genes expression level was significantly increased in NSCLC tissues, however methylation pattern of the target gene promoters, did not show any significant alteration.
These results indicate roles for miR-30d, miR-204-5p as tumor suppressor genes as well as target genes as oncogenes in NSCLC patients. Although these factors may have a significant role in NSCLC progression, further studies are necessary to investigate the implications of these findings for treatment of lung cancer.
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最近的研究表明自噬在包括肺癌在内的不同类型癌症中起作用。microRNAs 被认为是调节自噬相关基因的关键因素。miR-30d、miR-204-5p 和 miR-20a 是调控标记物,可以作为其靶基因抑制 beclin1、LC3、bcl2 和 ULK1 的表达,从而导致人癌细胞自噬减少。此外,表观遗传修饰 DNA 甲基化已被证明在癌症的不同阶段调节自噬。
在这项研究中,通过实时 qPCR 分析了 30 例非小细胞肺癌(NSCLC)患者肿瘤组织和相邻正常组织中 miR-30d、miR-204-5p 和 miR-20a 的表达水平,以及其靶基因的 DNA 甲基化。
与相邻正常组织相比,miR-30d(p 值=0.01)和 miR-204-5p(P=0.048)在肿瘤组织中明显下调,而 miR-20a 的表达水平没有明显变化。另一方面,靶基因的表达水平在 NSCLC 组织中显著增加,然而靶基因启动子的甲基化模式没有显示出任何显著的变化。
这些结果表明 miR-30d、miR-204-5p 作为抑癌基因以及靶基因作为癌基因在 NSCLC 患者中发挥作用。尽管这些因素可能在 NSCLC 的进展中具有重要作用,但仍需要进一步研究以探讨这些发现对肺癌治疗的意义。