Investigation On MicroRNA-mRNA Regulatory Mechanisms:a Pan-cancer Study

Micro RNAs(mi RNAs)are small,non-coding RNAs with 22 nucleotides in length.Substantial studies have shown that mi RNAs are closely related to cell growth,differentiation,proliferation,and apoptosis.Moreover,mi RNAs can regulate gene expression at the post-transcriptional level and play an important role in cancer development.At present,biological validation and computational prediction are two leading approaches for cancer mi RNA-m RNA regulatory mechanism study.However,very few of the studies investigated mi RNA-m RNA regulations from the pan-cancer angle.In this study,ten cancer types,including breast cancer,renal clear cell carcinoma,and lung adenocarcinoma,etc.,are selected for comparative analysis.Based on the regulatory pattern between biomarker mi RNAs and their target genes,we explore the role of mi RNA-m RNA regulations on cancer carcinogenesis.In methodology,through the collection of cancer mi RNA/m RNA expression profile data,bioinformatics identification of mi RNA biomarkers,target gene prediction,pathway enrichment analysis,etc.,this study aimed at identifying and comparing mi RNA biomarkers and mi RNA-m RNA associations across different cancer types.Firstly,differentially expressed(DE)mi RNAs/m RNAs were screened for each cancer and mi RNA biomarkers for each of the ten cancers were predicted using the in-house prediction model Mi RNA-BD.Based on cancer-specific mi RNA-m RNA network from the model,target genes of mi RNA biomarkers were inferred effectively.Key mi RNA-m RNA regulatory relationships associated with cancer progression were then extracted and validated.Finally,based on DEm RNAs and the targets of identified mi RNA biomarkers,pathway-level analysis for each cancer type were performed for systematic explanation of cancer homogeneity and heterogenicity problems.The results showed that the prediction model Mi RNA-BD had good generality and high accuracy for cancer mi RNA biomarker.At the molecular level,mi RNA biomarkers shared by different cancer types were screened,such as mi R-144-3p,mi R-125b-5p,mi R-21-5p,etc.Moreover,the expressions of some biomarker mi RNAs in different cancers tended to be heterogeneous according to previous reports.At the regulatory level,mi RNA-m RNA regulations shared by different cancers were also discovered,such as mi R-144-3p/KPN2 A,mi R-144-3p/CEP55,etc.Here some regulatory patterns,e.g.,mi R-144-3p/AHCY and mi R-141-3p/TCEAL2,were also found to be inconsistent across different cancer types.At the pathway level,cancer signaling(e.g.,p53 Signaling and ERK/MAPK Signaling),cardiovascular signaling(e.g.,Inhibition of Angiogenesis by TSP1)and immune response pathway(e.g.,IL-8 Signaling),showed the significance for cancer pathogenesis exploration.This study investigated the homogeneity and heterogenicity problems of cancers at molecular and systematical level,which had both theoretical and practical value.