Background
General background of evolutionarily conservative miR-15/107 family
Family behavior vs. individual signature
Aim of study
Methods
miRNA sequence alignment
Search for genomic position of miRNA host genes
miRNA-mRNA target relationship analysis
Analysis of multi-miRNA regulatory network
miRNA pathway analysis
Cell proliferation assay
Analysis of dysregulated miR-15/107 in disease
Results
The “AGCAGC” sequence for evolutionarily conservative miR-15/107 family
miRNAs | miRBase Accession Number | Sequence (from 5′ to 3′) |
---|---|---|
hsa-miR-15a-5p | MIMAT0000068 | UAGCAGCACAUAAUGGUUUGUG |
hsa-miR-15b-5p | MIMAT0000417 | UAGCAGCACAUCAUGGUUUACA |
hsa-miR-16-5p | MIMAT0000069 | UAGCAGCACGUAAAUAUUGGCG |
hsa-miR-103a-3p | MIMAT0000101 | AGCAGCAUUGUACAGGGCUAUGA |
hsa-miR-107 | MIMAT0000104 | AGCAGCAUUGUACAGGGCUAUCA |
hsa-miR-195-5p | MIMAT0000461 | UAGCAGCACAGAAAUAUUGGC |
hsa-miR-424-5p | MIMAT0001341 | CAGCAGCAAUUCAUGUUUUGAA |
hsa-miR-497-5p | MIMAT0002820 | CAGCAGCACACUGUGGUUUGU |
hsa-miR-503-5p | MIMAT0002874 | UAGCAGCGGGAACAGUUCUGCAG |
hsa-miR-646 | MIMAT0003316 | AAGCAGCUGCCUCUGAGGC |
hsa-miR-6838-5p | MIMAT0027578 | AAGCAGCAGUGGCAAGACUCCU |
Possible transcriptional pattern in clusters
miRNAs | Host gene | Transcript location | Chromosome position |
---|---|---|---|
hsa-miR-15a-5p | deleted in lymphocytic leukemia 2 (DLEU2) non-protein coding gene | Intron | chr13: 50049119–50,049,201 [−] |
hsa-miR-15b-5p | structural maintenance of chromosomes 4 (SMC4) protein-coding gene | Intron | chr3: 160404588–160,404,685 [+] |
hsa-miR-16-5p | structural maintenance of chromosomes 4 (SMC4) protein-coding gene | Intron | chr3: 160404745–160,404,825 [+] |
deleted in lymphocytic leukemia 2 (DLEU2) non-protein coding gene | Intron | chr13: 50048973–50,049,061 [−] | |
hsa-miR-103a-3p | pantothenate kinase 3 (PANK3) protein-coding gene | Intron | chr5: 168560896–168,560,973 [−] |
pantothenate kinase 2 (PANK2) protein-coding gene | Intron | chr20: 3917494–3,917,571 [+] | |
hsa-miR-107 | pantothenate kinase 1 (PANK1) protein-coding gene | Intron | chr10: 89592747–89,592,827 [−] |
hsa-miR-195-5p | mir-497-195 cluster host gene (MIR497HG) long non-coding RNA | N/A | chr17: 7017615–7,017,701 [−] |
hsa-miR-424-5p | MIR503 host gene (MIR503HG) long non-coding RNA | N/A | chrX: 134546614–134,546,711 [−] |
hsa-miR-497-5p | mir-497-195 cluster host gene (MIR497HG) long non-coding RNA | N/A | chr17: 7017911–7,018,022 [−] |
hsa-miR-503-5p | MIR503 host gene (MIR503HG) long non-coding RNA | N/A | chrX: 134546328–134,546,398 [−] |
hsa-miR-646 | MIR646 host gene (MIR646HG) long non-coding RNA | N/A | chr20: 60308474–60,308,567 [+] |
hsa-miR-6838-5p | polymerase (DNA) mu (POLM) protein-coding gene | Exon of transcript variant 2, intron of transcript variant 1 and 3 | chr7: 44073378–44,073,433 [−] |
Interaction of miR-15/107 family and their target genes
Collective effects of target regulation from the miR-15/107 family
Pathway analysis of the miR-15/107 family
Cell cycle as a representative pathway regulated by the miR-15/107 family
Members of the miR-15/107 gene family have an inhibitory effect on cell proliferation
Dysregulation of miR-15/107 in diseases and prospect of therapeutics
miR-15a | miR-15b | miR-16 | miR-103 | miR-107 | miR-195 | miR-424 | miR-497 | miR-503 | sum | |
---|---|---|---|---|---|---|---|---|---|---|
Adrenocortical carcinoma | - | - | - | - | - | - | - | - | √ | 1 |
Alzheimer's disease | √ | - | - | - | √ | - | - | - | - | 2 |
Acute lymphoblastic leukemia (ALL) | - | - | - | - | - | - | √ | - | - | 1 |
Acute myeloid leukemia (AML) | - | √ | - | √ | - | √ | √ | - | - | 4 |
Acute promyelocytic leukemia (APL) | √ | √ | - | - | - | - | - | - | - | 2 |
Autism spectrum disorder (ASD) | √ | √ | - | - | - | - | - | - | - | 2 |
B-cell chronic lymphocytic leukemia | - | √ | - | - | - | - | - | - | - | 1 |
Bladder cancer | - | - | - | - | - | √ | - | - | - | 1 |
Breast cancer | - | - | - | - | - | √ | - | √ | - | 2 |
Cardiac hypertrophy
| - | √ | - | √ | √ | √ | √ | - | - | 5 |
Cerebellar neurodegeneration | - | - | - | √ | - | - | - | - | - | 1 |
Chronic lymphocytic leukemia (CLL)
| √ | - | √ | - | √ | √ | √ | - | - | 5 |
Chronic pancreatitis | - | - | - | - | - | √ | - | √ | - | 2 |
Colorectal cancer | - | √ | - | - | √ | √ | - | √ | - | 4 |
Endometriosis | - | - | - | - | - | - | √ | - | - | 1 |
Epithelial ovarian cancer (EOC) | - | - | - | √ | - | - | - | - | - | 1 |
Esophageal cancer | - | - | - | √ | √ | - | - | - | - | 2 |
Gastric cancer (stomach cancer) | - | √ | √ | √ | √ | - | - | - | - | 4 |
Glioma | √ | √ | √ | - | - | - | - | - | - | 3 |
Heart failure | - | - | - | - | - | √ | - | - | - | 1 |
Head and neck squamous cell carcinoma (HNSCC) | √ | - | - | - | - | √ | √ | - | - | 3 |
Hepatocellular carcinoma (HCC) | √ | - | √ | - | √ | √ | - | - | - | 4 |
Hodgkin's lymphoma | - | - | √ | - | - | - | - | - | - | 1 |
Intrahepatic cholangiocarcinoma (ICC) | - | - | - | - | - | - | √ | - | - | 1 |
Kidney cancer | √ | - | - | - | - | - | √ | - | - | 2 |
Lung cancer | - | - | √ | - | - | √ | - | √ | - | 3 |
Lupus nephritis | - | √ | - | - | - | √ | - | - | - | 2 |
Malignant melanoma | √ | - | - | - | √ | - | - | - | - | 2 |
Non-alcoholic fatty liver disease (NAFLD) | - | - | - | √ | √ | - | - | - | - | 2 |
Non-small cell lung cancer (NSCLC) | √ | √ | √ | - | √ | - | - | - | - | 4 |
Ovarian cancer (OC) | √ | - | √ | - | - | √ | √ | - | - | 4 |
Oral Squamous Cell Carcinoma (OSCC) | - | - | √ | - | √ | - | - | - | - | 2 |
Pancreatic cancer | - | √ | - | √ | √ | - | √ | - | - | 4 |
Papillary thyroid carcinoma (PTC) | √ | - | √ | - | - | - | - | - | - | 2 |
Pituitary adenoma | √ | - | - | √ | - | - | - | - | - | 2 |
Polycystic Kidney Disease | √ | - | - | - | - | - | - | - | - | 1 |
Polycystic liver disease | √ | - | - | - | - | - | - | - | - | 1 |
Prostate cancer
| √ | - | √ | √ | - | √ | - | √ | √ | 6 |
Retinoblastoma | - | - | - | - | - | - | - | - | √ | 1 |
Schizophrenia | √ | √ | - | - | √ | √ | - | - | - | 4 |
Serous ovarian cancer | - | - | √ | - | - | - | - | - | - | 1 |
Ulcerative colitis (UC) | - | - | √ | - | - | √ | - | - | - | 2 |
Total (42) | 17 | 12 | 13 | 10 | 13 | 16 | 10 | 5 | 3 |