Table 1.
The characteristics of the included studies.
| Regulatory Axis | Samples | Methods | Disease | Key Findings | References |
|---|---|---|---|---|---|
| miR-29/B7-H3 | Human Burkitt lymphoma cell line Daudi, HeLa, LAN-1,NB1691, solid tumor samples (15 brain tumors, 5 hepatoblastomas, 41 neuroblastomas, 11 sarcomas, and 5 Wilms’ tumors) and 18 normal tissues |
Monoclonal antibodies, whole-cell lysates, Western blot, subcellular fractionation, 8H9 antigen affinity purification, (q)RT-PCR, immunofluorescence, and luciferase reporter assay | Human cancers | Downregulation of miR-29 isoforms. Inverse regulation of B7-H3 by miR-29. Immune escape in solid tumors. |
[48] |
| miR-187/B7-H3 | Blood and tissue | qRT-PCR, luciferase reporter assay, dimethylthiazol-diphenyltetrazolium bromide (MTT) assay, tumorigenicity assay, and scratch assay |
Clear cell renal cell carcinoma | Downregulation of miR-187 in clear-cell renal cell carcinoma. Association with lower survival in patients. Inverse regulation of B7-H3 by miR-187. Overexpression of miR-187 inhibits cell growth and migration. |
[52] |
| miR-29c/B7-H3 | Melanoma tissue and cell lines, i.e., M-1, M-101, M-111, M-12, M-14, JK-0346 Mel-B, JH-1173, and Wm266–4 | IHC analysis, immunofluorescence, RT-qPCR assay, Western blotting, development of B7-H3-knockdown cells, development of B7-H3-overexpressing cells, colony formation, invasion assay, and cell migration |
Cutaneous melanoma | Tumor suppressor function of miR-29c. miR-29c directly targets B7-H3. Overexpression of B7-H3 increased cell migration and invasion. |
[41] |
| miR-29c/B7-H3, miR-892a/B7-H3, miR-363/B7-H3, miR-940/B7-H3, miR-214/B7-H3, miR-34b/B7-H3, miR-665/B7-H3, miR-593/B7-H3, miR-885–3p/B7-H3, miR-124a/B7-H3, miR-326/B7-H3, miR-601/B7-H3, and miR-708/B7-H3 | JIMT-1 cell line, KPL-4 cell line, and breast cancer tumor |
Microarray screening and data analysis, immunoblotting, luciferase assays, qRT-PCR |
Breast cancer | Western immunoblotting validated the 20 most effective miRs ((hsa-miR-892a, hsa-miR-380–5p, hsa-miR-125b-2, hsa-miR-363, hsa-miR-940, hsa-miR-214, hsa-miR-34b, hsa-miR-665, hsa-miR-593, hsa-miR29c, hsa-miR-555, hsa-miR-885–3p, hsa-miR-567, hsa-miR-297, hsa-miR-187–3p, hsa-miR-124a-1, hsa-miR-326, hsa-miR-601, hsa-miR-506, and hsa-miR-708) that can downregulate B7-H3 expression in the JIMT-1 cells. Thirteen miRs directly targeted B7-H3. miR-29c levels were low, whereas B7-H3 had a relatively high expression. The high miR-29c expression is associated with increased survival. |
[35] |
| miR-29a/B7-H3 | CL021, CL043, CL044, CL013, and tissue samples. | Sequencing, statistical analysis of differential miR expression, and qRT-PCR |
Central nervous system (CNS) neuroblastoma | Low expression of miR-29a among pre-CNS primaries and CNS metastasis compared to non-CNS. B7-H3 expression was targeted by miR-29a. |
[28] |
| miR-124/B7-H3 | Tumor samples and mg-63 cell line |
Dual-luciferase reporter assay qRT-PCR and Western blotting analysis | Osteosarcoma (OS) | Downregulation of miR-124 in clinical OS specimens associated with advanced clinical stage and pulmonary metastasis. miR-124 directly targets B7-H3. Overexpression of B7-H3 abolished the reduction of cell growth and invasion. |
[42] |
| miR-155/CEBPB/miR-143/B7-H3, miR-145/B7-H3, miR-192/B7-H3, miR-378/B7-H3 miR-155/CEBPB/miR-143/B7-H4 |
tissue samples, including cancer and adenoma tissues; Caco-2, HCT-116, LoVo, Jurkat, SW480, SW620, and CHO cell lines |
Gene silencing, microRNA array, construction of miR–miR functional synergistic network, KEGG pathway enrichment analysis, qRT-PCR, immunohistochemistry, cell lysates and cell fractionations, Western blot, immunofluorescence, and ELISA and MTT assay |
Colorectal cancer (CRC) | The miR-155 node was the largest in CRC. Elevated the B7-H4 and B7-H3 expression in adenoma tissues. miR-155 abated miR-143 expression through the transcription factor CCAAT enhancer binding protein beta (CEBPB). MiR-143 inhibited the growth of CRC cells. The lowly-expressed miR-192, miR-378, and miR-145 contributed to the B7-H3 over-expression in colorectal cancer, consequently leading to cancer immune evasion. |
[53] |
| miR-187/B7-H3 | A total of 32 pairs of colorectal tumor and matched nontumor tissues and 80 CRC tissues. Human CRC cell lines SW1116, SW480, SW620, HT29, LOVO, and the normal colonic epithelial cell line NCM460. | Real-time PCR, cell proliferation assay, transwell cell migration, invasion assay, apoptosis assay, miR target prediction, Western blotting, plasmid construction, and luciferase reporter assays |
Colorectal cancer | Decreased miR-187 expression shorter overall survival and relapse-free survival of patients with CRC. B7-H3, is negatively correlated miR-187 level in CRC cells. |
[45] |
| miR-539/B7-H3 | Cell lines: U87 and U251, normal human astrocytes |
Cell viability assay, real-time PCR, colony formation, Western blotting, and luciferase assays | Human gliomas | Increased B7-H3 expression and downregulation of miR-539 glioma cell lines. B7-H3 repression by miR-539 suppresses cell proliferation in human gliomas. |
[34] |
| miR-29c/B7-H3 | Peripheral blood samples, human monocyte cell line THP-1 |
Microarray analysis of miRs, luciferase reporter assay, immunofluorescence staining, qRT-PCR, and plasma B7-H3 detected by ELISA |
Allergic asthma | The lower level of miR-29c and a higher level of plasma B7-H3 in children with asthma exacerbation. The function of miR-29c on macrophage in regulating T cell differentiation. miR-29c is correlated to its target gene B7-H3. |
[51] |
| miR-29/B7-H3 | From the CGGA dataset, we collected RNA-Seq data for 325 samples, ranging from WHO grade II to grade IV. In the TCGA dataset, RNA-Seq data were available for 669 samples. | Detection of isocitrate dehydrogenase mutation and defining immune pathways |
Diffuse brain glioma | Regulation of B7-H3 by methylation and miR-29 family at different stages, respectively. Association of B7-H3 with higher malignancy and development and the progression of gliomas |
[29] |
| miR-29c/B7-H3 | Human CRC cell lines SW620 and HCT116 and human colonic epithelial cell line FHC | Cell viability assay, cell cycle assay, RT-PCR, Western blot, cycloheximide chase assay, and dual-luciferase reporter assay | Colorectal cancer | Downregulation of miR-29c in many cancer types; miR-29c directly binds to B7-H3 mRNA and suppresses B7-H3 expression. Astragaloside IV treatment downregulated B7-H3 via the elevation of miR-29c. |
[44] |
| miR-506/B7-H3 | Bone marrow mononuclear cells were isolated from 12 de novo mantle cell lymphoma (MCL) patients with bone marrow involvement. Human MCL cell lines Maver and Z138. |
qRT-PCR, Western blotting, transfection and lentivirus infection, dual-luciferase assay, cell proliferation assays, cell cycle assays, cell migration, and transwell invasion assays |
Mantle cell lymphoma | Overexpression of B7-H3 and downregulation of miR-506 in MCL patients. miR-506 inhibits the proliferation and invasion of MCL cells by targeting B7-H3. miR-506 induced MCL cell cycle arrest in the G0/G1 phase and repressed MCL cell migration. |
[54] |
| miR-187/B7-H3 | HaCaT cell line and psoriatic skin samples. |
qRT-PCR, cell viability assay, Western blot analysis, RNA transfection, luciferase reporter assays, B7-H3 overexpression (vector), histological analysis, immunohistochemistry, and cell cycle analysis |
Psoriasis | Downregulation of miR-187 in the cytokine-stimulated keratinocytes compared with corresponding normal controls. Decreased miR-187 level in psoriatic skin compared with adjacent, uninvolved psoriatic skin. B7-H3 is a direct molecular target of miR-187. Upregulation of B7-H3 level in psoriatic skin. |
[39] |
| MYC/miR-29/B7-H3 | Five human medulloblastoma (MB) tumor tissues; D283 Med, D425 Med, D458 med cell line, and human umbilical vein endothelial cells (HUVECs). |
In silico analysis, ELISA, human angiogenesis array, immunoblotting, gelatin zymography, F-actin staining and immunostaining, RT-PCR and RNA-Seq, immuno-paired antibody detection analysis, chromatin immunoprecipitation and DNA sequencing, fluorescence-activated cell sorting analysis, in vitro angiogenesis assay, and chick chorioallantoic membrane assay |
Medulloblastoma | Association of B7-H3 high expression with poor survival in MB patients. B7-H3 promotes angiogenesis in MB cells. miR-29 exhibits global anti-tumor functions and promotes STAT1 activation. Induces apoptosis via miR-29 in combination with MYC inhibition. |
[37] |
| miR-1301–3p/B7-H3, miR-335–5p/B7-H3 miR-28–5p/B7-H3 |
Serum samples from patients with colorectal cancer | ELISA, analysis of predicted putative miRs, and RT-PCR |
Colorectal cancer | Upregulation of serum B7-H3 expressions in CRC patients. B7-H3 was predicted to be a target of miR-1301–3p, miR-335–5p, and miR-28–5p. Decrease serum miR-28–5p, miR-1301–3p, and miR-335–5p expressions in stage III and IV disease compared to stage I and II. These miRs are negatively related to the advanced TNM stages. |
[43] |
| lncRNA NEAT1/miR-214/B7-H3 | Bone marrow samples from 30 multiple myeloma patients and multiple myeloma cells, i.e., line RPMI 8226, and human monocyte cell line THP-1. | Dual-luciferase reporter assay, RNA immunoprecipitation assay, ELISA assay, Western blotting, and RT-qPCR |
Multiple myeloma (MM) | Increase the level of long non-coding RNA (lncRNA) NEAT1 and B7-H3. Downregulation of miR-214 expression occurred in multiple myeloma tissues. lncRNA NEAT1 directly targeted miR-214 to promote M2 macrophage polarization by upregulating B7-H3 in MM. |
[30] |
| miR-29c/B7-H3/Th17 | Peripheral blood and nasopharyngeal secretions samples, and human monocytic cell line THP-1 |
Quantitative ELISA-specific M. pneumoniae immunoglobulin G (IgG) and immunoglobulin M (IgM), real-time PCR for M. pneumoniae detection, multiple pathogen detection, examination of soluble B7-H3 and IL-17 in plasma, immunofluorescence staining, and luciferase assay |
Mycoplasma pneumoniae pneumonia (MPP) | The lower level of miR-29c and a higher level of B7-H3 and IL-17 in children with MPP. B7-H3 is the direct target of miR-29c, and miR-29c silencing or overexpression could up- or downregulate the expression of B7-H3 in THP-1 cells. |
[33] |
| miR-1253/B7-H3 | All tumor samples were obtained from patients in the pediatric age group, with DAOY, D283, D341, D425, D556, D458, and HDMB03 cell lines. |
PCR, cell proliferation assay, colony formation assay, cell migration and invasion, wound healing, annexin V-FITC/PI analysis, Western blotting, dual-luciferase reporter assay, target prediction in situ hybridization, immunohistochemistry, DNA methylation profiling and tumor classification, and de-methylation studies |
Medulloblastoma | Deregulation of miR-1253 expression in medulloblastoma. miR-1253 inhibits mediators of cellular proliferation and promotes tumor cell apoptosis. B7-H3 is oncogenic target of miR-1253. High expression of B7-H3 in tumor samples. Both miR-1253 restoration and B7-H3 silencing reduce the migratory and invasive medulloblastoma cells. |
[32] |
| miR-145/B7-H3 | Pleural effusion | Observational indexes and qRT-PCR | Lung cancer | The higher expression level of B7-H3 in lung cancer. Lower expression level of miR-145 in the pleural effusion of the study group than in the control group. Relationship with lymphatic metastasis, differentiation degree, and TNM stage. |
[31] |
| miR-199a/B7-H3 | HeLa, C4–1, SiHa, CaSki, and C-33A |
Cell proliferation assay, luciferase reporter assays, enzyme-linked immunosorbent assay, Western blot assays, qRT-PCR, cell migration, invasion assay, and immunohistochemical staining |
Cervical cancer (CC) | miR-199a was expressed at lower levels in CC tissues than in adjacent normal tissues. miR-199a inhibits cell proliferation, migration and the invasion of CC cells by targeting B7-H3. The expression level of B7-H3 was significantly upregulated in CC tissues. |
[50] |
| miR-1207–5p/B7-H4 | Whole blood samples | Selection of miR single-nucleotide polymorphisms (SNPs), SNP genotyping, selection of miR SNPs from published databases, and luciferase reporter assay |
Colorectal cancer | Upregulation of miR-1207–5p in CRC tissues. miR-1207–5p can suppress the expression of B7-H4 molecule by binding with the rs13505 G-allele-specific 3’-UTR of B7-H4 gene, which is impacted by the rs13505. |
[46] |
| 62 different miRs * | L3.6p1 cells, which were derived from a human pancreatic carcinoma | Bioinformatics analysis and miR microarray analysis | Pancreatic cancer | miRs participate in the B7-H4-mediated regulation of oncogenicity and pathogenesis of pancreatic cancer. | [38] |
| miR-125a-5p/B7-H5 | Cell lines MCF10A, MDA-MB-468, MDA-MB-231, MCF7, MKN28, SNU1, MKN45, AGS, SW480, HCT116, HT29, and RKO, as well as gastric tumors | RNA extraction, expression quantification; DNA extraction, methylation analysis; short-interference-RNA experiments; BMP4 treatment; and antimiR experiments |
Gastric cancer (GC) |
B7-H5 expression loss is a recurrent event in GC, caused by promoter methylation and/or miR-125a-5p overexpression, and GC-microenvironment myofibroblasts overexpress B7-H5. B7-H5 expression is under the control of miR-125a-5p, as its targeted inhibition led to an overexpression of B7-H5. |
[36] |
| miR-16/B7-H5 | Colon tissue | miR microarray analysis, gene microarray analysis, qRT-PCR, miR target gene prediction, and luciferase reporter assays |
Active Crohn’s disease | Upregulation of miR-16 in the inflammatory areas of the ascending colon mucosa. Inhibition of B7-H5 expression. Immune inflammatory responses in the ascending colon. Reduction in miR-16 expression suggests the possibility of canceration of the inflammatory colon. hsa-miR-16–1 directly regulated the human B7-H5 gene. |
[47] |
| miR-93/B7-H6, miR-340/B7-H6, miR-195/B7-H6 | The data were from TCGA data from 1092 patients with breast cancer, including gene expression, miR expression, and survival data. Human breast cancer cell lines, i.e., MCF7, MDA-MB-231, SK-BR-3, and human fibrocystic disease epithelium cell line MCF10A. |
TCGA breast cancer transcriptome profiling analysis, sorting analysis of the most likely miRs targeting the B7 family, and qRT-PCR |
Triple-negative breast cancer | Upregulation of B7-H6 in breast cancer based on an analysis of the TCGA database. A high level of B7-H6 suggested a worse prognosis. Bioinformatic analysis predicted that miR-93, miR-195, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and they exert this function by targeting B7-H6. |
[49] |
| miR-3116/B7-H7, miR-6870–5p/B7-H7 | Clinical and experimental data from multiple databases, including cBioPortal, TCGA, Cistrome, TIMER, Oncomine, Kaplan–Meier, GeneXplain. | Expression profiling of B7-H7 in human cancers, pan-cancer survival analysis, and bioinformatics analysis for understanding the regulatory mechanism of B7-H7 | Clear cell carcinoma | The bioinformatic view showed that basic leucine zipper ATF-like transcription factor (BATF) in B lymphocyte and SMAD in monocytes might be responsible for the dysregulation of B7-H7 in kidney renal clear cell carcinoma (KIRC). miR-3116 and miR-6870–5p may have a role in the regulation of B7-H7. |
[40] |
qRT-PCR: quantitative reverse transcription polymerase chain reaction, ELISA: enzyme-linked immunosorbent assay, miR: microRNA, KEGG: The Kyoto Encyclopedia of Genes and Genomes. * 62 miRs are reported in the Results section under B7-H4.