Identification and Elucidation of the Protective IsomiRs in Lung Cancer Patient Prognosis

MicroRNAs (miRNAs) are approximately 20-22 nucleotides in length, which are well known to participate in the post-transcriptional modification. The mature miRNAs were observed to be varied on 5' or 3' that raise another term-the isoforms of mature miRNAs (isomiRs), which have been proven not the artifacts and discussed widely recently. In our research, we focused on studying the 5' isomiRs in lung adenocarcinoma (LUAD) in The Cancer Genome Atlas (TCGA). We characterized 75 isomiRs significantly associated with better prognosis and 43 isomiRs with poor prognosis. The 75 protective isomiRs can successfully distinguish tumors from normal samples and are expressed differently between patients of early and late stages. We also found that most of the protective isomiRs tend to be with downstream shift and upregulated compared with those with upstream shift, implying that a possible selection occurs during cancer development. Among these protective isomiRs, we observed a highly positive and significant correlation, as well as in harmful isomiRs, suggesting cooperation within the group. However, between protective and harmful, there is no such a concordance but conversely more negative correlation, suggesting the possible antagonistic effect between protective and harmful isomiRs. We also identified that two isomiRs miR-181a-3p|-3 and miR-181a-3p|2, respectively, belong to the harmful and protective groups, suggesting a bidirectional regulation of their originated archetype-miR-181a-3p. Additionally, we found that the protective isomiRs of miR-21-5p, which is an oncomiR, may be evolved as the tumor suppressors through producing isomiRs to hinder metastasis. In summary, these results displayed the characteristics of the protective isomiRs and their potential for developing the treatment of lung cancer.