The Regulatory Cross-Talk between microRNAs and Novel Members of the B7 Family in Human Diseases: A Scoping Review

Abstract

The members of the B7 family, as immune checkpoint molecules, can substantially regulate immune responses. Since microRNAs (miRs) can regulate gene expression post-transcriptionally, we conducted a scoping review to summarize and discuss the regulatory cross-talk between miRs and new B7 family immune checkpoint molecules, i.e., B7-H3, B7-H4, B7-H5, butyrophilin like 2 (BTNL2), B7-H6, B7-H7, and immunoglobulin like domain containing receptor 2 (ILDR2). The current study was performed using a six-stage methodology structure and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Embase, Scopus, Cochrane, ProQuest, and Google Scholar were systematically searched to obtain the relevant records to 5 November 2020. Two authors independently reviewed the obtained records and extracted the desired data. After quantitative and qualitative analyses, we used bioinformatics approaches to extend our knowledge about the regulatory cross-talk between miRs and the abovementioned B7 family members. Twenty-seven articles were identified that fulfilled the inclusion criteria. Studies with different designs reported gene-miR regulatory axes in various cancer and non-cancer diseases. The regulatory cross-talk between the aforementioned B7 family molecules and miRs might provide valuable insights into the pathogenesis of various human diseases.

Keywords: B7; cancer; gene therapy; human diseases; immune checkpoint; immunotherapy; microRNA.

Figure 1

Search strategy flow chart based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.

Figure 2

Enriched KEGG pathways of predicted miRs obtained from the miRDB database. Enriched pathways with at least two associated miRs were shown. The color of individual fields represents the −log10-transformed p-value of the respective enrichment results. Darker colors indicate more significant associations between an miR and the target pathway. Enriched KEGG pathways in the category of immune system are indicated by blue arrows.

Figure 3

The predicted gene-miR-pathway network. Cytoscape v3.8.0 software was used for evaluating gene–miRNA interaction, and their corresponding immune-related pathways via their visualization as a network. Ellipse, triangle, and round rectangle represent pathway, miR, and gene, respectively.