Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
Oncol Rep. 2013 Dec;30(6):2945-56. doi: 10.3892/or.2013.2762. Epub 2013 Oct 1.
Lung cancer (LC) is the leading cause of cancer-related mortality worldwide. However, few studies of its specific mechanisms useful for diagnosis or treatment exist. microRNAs (miRNAs) present one mechanism through which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, LC-associated pathways targeted by LC-related miRNAs (LC-miRNAs) remain completely unknown. In the present study, we investigated 8 LC-miRNAs previously identified as regulators in three molecular subtypes of LC. The results showed that LC-miRNAs may post-transcriptionally function mainly through manipulating the expression of nucleic acid binding proteins and transcription factors, and target genes for the LC-miRNAs were most prominently predicted to function in regulation of transcription. Our analysis also highlighted the potential of these LC-miRNAs to regulate the cell differentiation, proliferation, endocytosis and migration signaling logically required to cause an LC cell mainly through five canonical pathways (PI3K-Akt signaling pathway, pathways in cancer, MAPK signaling pathway, HTLV-I infection and focal adhesion). These findings may form a useful basis for potential future development of novel LC therapeutic treatments.
肺癌（LC）是全球癌症相关死亡的主要原因。然而，目前针对其具体机制（有助于诊断或治疗）的研究甚少。microRNAs（miRNAs）是一种机制，通过该机制，具有多种功能的基因可以在多个途径的转录后水平上被同时调控。然而，LC 相关 miRNA（LC-miRNAs）靶向的 LC 相关途径仍然完全未知。在本研究中，我们研究了先前在 LC 的三个分子亚型中鉴定为调节剂的 8 种 LC-miRNAs。结果表明，LC-miRNAs 可能主要通过操纵核酸结合蛋白和转录因子的表达来发挥转录后功能，并且 LC-miRNAs 的靶基因最显著地预测为在转录调控中发挥作用。我们的分析还强调了这些 LC-miRNAs 调节细胞分化、增殖、内吞和迁移信号的潜力，这些信号逻辑上需要导致 LC 细胞主要通过五个经典途径（PI3K-Akt 信号通路、癌症途径、MAPK 信号通路、HTLV-I 感染和黏着斑）。这些发现可能为未来潜在的 LC 治疗方法的开发提供有用的基础。
