MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis
Abstract
:1. Introduction
- (“neoplasm invasiveness/etiology”[MeSH Terms]) AND specific microRNA,
- ((“obesity”[MeSH Terms]) OR (“insulin resistance”[MeSH Terms])) OR (“metabolic syndrome”[MeSH Terms]) AND specific microRNA.
2. MicroRNAs Link the Metabolic Syndrome and Cancer
2.1. The Role of miRNAs in Cancer by Modulating Macrophage Phenotypes
2.2. The Role of CTBP1 in Cancer by Modulating microRNAs Expression
2.3. The Role of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Obesity and Cancer
2.4. PI3K/AKT—Common Pathway in MetS and Cancer
2.5. Caveolin-1 (CAV1) Signaling
2.6. Wnt/β-catenin Signaling
2.7. PTEN Signaling
2.8. The miRNA-Processing Enzyme DICER
2.9. PPARα -FOXP4- NOTCH Pathway
2.10. SRC/SOX2/c-MYC Pathway
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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miRNAs | Target Genes and Functions in Obesity/IR/MeS | Target Genes or Pathway in Cancer | Type of Cancer (Oncomir/Tumor Suppressor) | References for Cancer Genes or Pathway |
---|---|---|---|---|
miR-21 | TIMP3 PPAR-c, GLUT4 PTEN/PI3K/Akt pathway; STAT3, TGFRB2, PTEN, Sprouty1 and Sprouty 2 | RhoB | HCC, Breast cancer ↑ | [96] |
PDCD4 and Maspin | Prostate cancer ↑ | [97,98] | ||
Prostate cancer ↓ | [99] | |||
AKT/ERK pathways | HCC ↑ | [100] | ||
RECK | Osteosarcoma ↑ | [101] | ||
CASC7 and IGN3 | Colorectal cancer ↑ | [102] | ||
PTEN | Colorectal cancer ↑ | [103] | ||
RhoB | Colorectal cancer ↑ | [104] | ||
Sec23A | Colorectal cancer ↑ | [105] | ||
TIMP-3 and RECK | Colorectal cancer ↑ | [105] | ||
STAT3, PIK3R1 | Breast cancer ↑ | [106,107] | ||
PTEN | NSCLC ↑ | [108] | ||
VHL/PI3K/AKT | Papillary thyroid cancer ↑ | [109] | ||
PTEN and PDCD4 | Gastric cancer ↑ | [110] | ||
TIMP3 | Melanoma ↑ | [111] | ||
Sox2/β-catenin, RECK | Glioma ↑ | [112,113] | ||
PTEN, DKK, BCL2 | OSCC ↑ | [114,115,116] | ||
PTEN | Cervical cancer ↑ | [117] | ||
RCC ↑ | [118] | |||
miR-24-3p | SR-B1, HMGCR, DHCR24, SREBP2 KCNQ1 | LPAATβ | Osteosarcoma ↓ | [119] |
CCK8 | Colorectal cancer ↓ | [120,121] | ||
p27Kip1, Bim | Breast cancer ↓ | [122,123] | ||
miR-26a | GSK3β, PKCδ, PKCθ, ACSL3, ACSL4, PCK1, TCF7L2, FXl19 | p53, SMAD1, EZH2, IL-6-Stat3, CTDSP1/2/L, SODD, CKS2, FGF9 | Lung, breast, HCC, rabdomyosarcoma, prostate, melanoma, papillary thyroid, gastric, pancreatic cancer ↓ | [124] |
MCL-1 BRCA1 | Breast cancer ↓ Triple-negative BC↓ | [125] [126] | ||
PTEN and PHB, ERα, GSK3 | Glioma, ovarian cancer, colon cancer, cholangiocarcinoma ↑ | [124] | ||
miR-26b | Glut 4, PTEN/PI3K/AK, Fbxl19 | Cox-2 | Glioma, NSCLC ↓ | [127,128] |
EphA2 | HCC ↓ | [129] | ||
miR-27 | PPAR-γ, Wnt1, GLUT-4 PI3K, PRDM16, PPARα, CREB, PGC1β | ZEB1, ZEB2, Slug, Vimentin, E-cadherin | Gastric cancer ↓ | [130] |
MDR1/P-glycoprotein | Cancer cells ↑ | [130] | ||
SPRY1, BAK, FOXO1, CBLB/GRB2 | Breast cancer ↓ | [131,132] | ||
miR-27b | PHB, INSR, PPARγ | PPARγ | CRC ↑ | [37] |
CDH11, EMT, PPARγ- NHE1 pathway | Cervical cancer ↑ | [39,133] | ||
LIMK1, Sp1 | NSCLC ↓ | [48,134] | ||
miR-30 | DDL40-Notch-1 | Breast cancer ↑ | [135] | |
MMP19 | NSCLC ↑ | [136] | ||
Fibronectin, Vimentin, N-cadherin | Pancreatic cancer ↑ | [137] | ||
miR-31 | PPARg, PRKAA1, ACACA, GLUT4, IRS1, HIF-1a | ARIDIA | HNSCC ↑ | [138] |
Rectal cancer ↑ | [139] | |||
FIH-1 | CRC ↑ | [140] | ||
RhoA, GNA13 | Breast cancer ↑ | [140,141] | ||
PPP6C | Mezothelioma ↓ | [142] | ||
Dock1, NF-jB/Snail | Glioma ↓ | [143] | ||
ZH2, p53 pathway | Gastric, ovarian, osteosarcoma, prostate cancer ↓ | [63,144] | ||
miR-34a | Inhibit macrophage M2 induced adipose inflammation | BCL-2 and SIRT1 | Breast cancer↓ | [145] |
Notch1 | Breast cancer↓ | [146] | ||
Wnt/β-catenin signaling pathway | Breast cancer↓ | [147] | ||
Fra-1 | Breast cancer↓ | [148] | ||
MYC, P53 | Breast cancer↓ | [149,150] | ||
E2F3 | Neuroblastoma ↓ | [151] | ||
c-Met and β-catenin | Colon cancer ↓ | [152] | ||
P53 | Osteosarcoma ↓ | [153] | ||
MET, P53 | Ovarian cancer ↓ | [154,155] | ||
CD44 | Prostatic cancer ↓ | [156] | ||
AXL | Solid cancer ↓ | [157,158] | ||
miR96 | INSR, IRS | SOX6, EphrinA5 | HCC ↑ | [159,160] |
PTPN9, FOXO1, FOXO3a | Breast cancer ↑ | [161,162,163] | ||
FOXO3 | NSCLC ↑ | [164] | ||
RECK | ESCC ↑ | [165] | ||
AEG-1 | Glioblastoma ↓ | [166] | ||
Ezrin | RCC ↓ | [167] | ||
KRAS | Pancreatic cancer ↓ | [168] | ||
miR-100 | mTOR, IGFR, VLDLR | Bladder cancer | [169] | |
HOXA1, Rac1, ICMT, EphB6, AGO2, Plk1, Wnt, β-catenin or RBSP3 | HCC, RCC, bladder cancer, NSCLC, and epithelial ovarian cancer | [170] [171] | ||
mTOR kinase | Endometrioid endometrial carcinoma | [171] | ||
CRC | [172] | |||
miR-125b | PI3K/AKT JNK signaling pathway, SIRTs | NF-κB, | DLBCL ↑ | [173] |
MAPK11, IRF4, TET2-VEGFA | Acute leukemia ↑ | [174] | ||
Wnt, PI3K/Akt, STAT-3, MAPK, NF-κB, p53 | HCC, CRC, RCC, thyroid larynx, osteosarcoma, prostate melanoma, Ewing sarcoma, glioblastoma, gallbladder, ovarian cancer | [175] | ||
miR-126 | IRS-1, CCL2 | PI3K, KRAS, EGFL7, CRK, ADAM9, HOXA9, IRS-1, SOX-2, SLC7A5 and VEGF | Gastrointestinal tract, genital tracts, breast, thyroid, lung cancers | [176] |
NSCLC | [177] | |||
CRC | [176] | |||
RCC | [176] | |||
miR-143 | ORP8/insulin-AKT pathway, PPARg and aP2 Leptin | Bcl2, ERK5, KRAS | Cervical, prostate, CRC ↓ | [178] |
ERBB3 | Breast cancer ↓ | [179] | ||
KRAS, Vimentin, CXCR4, MMP-9 | Breast cancer ↓ | [180] | ||
FAM83F | Esophageal squamous cell carcinoma ↓ | [181] | ||
DNMT3A | Gastric cancer ↓ | [182] | ||
TLR2, NF-κB, MMP-2, MMP-9, CD44, MMP14, integrin β1, integrin β4 | HCC ↓ | [183] | ||
PAI-1/MMP-13 | Osteosarcoma ↓ | [184] | ||
Smad3, CD44, and K-Ras | NSCLC ↓ | [185] | ||
miR-145 | AKT/PI3K/GLUT4 ADAM22, MYO5A, LOX, and GM2A | PI3K/AKT, MRP1, SMAD, KLF4, c-myc, Ets1, E-cadherin, FSCN1, BCL2 | BC, gastric, CRC, NSCLC, glioma, HCC, osteosarcoma, ovarian, cervical, prostate, bladder, nasopharyngeal cancer ↓ | [186] |
miR-148a-3p | inhibit DNMT1 | DNMT1 | Esophageal Cancer↓ | [187] |
WNT5A, TGF-α, BTG2 and MYCBP | Chordoma ↑ | [188] | ||
miR-155 | C/EBPβ, HDAC4, PPARγ, GLUT4, IRS1, PPAR-c, Creb1, Cebpb, Pparg, Pnpla2, Fabp4, Fasn, AdipoQ, | TNF∝, NF-kB pathway, ERK pathway, Caspase 3 | Osteosarcoma ↑ | [189] [190] |
RhoA, PEG10 and MYB | Breast cancer ↑ | [191,192] | ||
Gallbladder cancer ↑ | [193] | |||
NDFIP1 | Melanoma ↑ | [194] | ||
FGF2 | ESCC ↑ | [195] | ||
Nasopharyngeal carcinoma ↑ | [196] | |||
IGF-1 | Colon cancer ↑ | [197] | ||
181c-3p | PPARα; reduced inhibition of PPARα, BC proliferation | PPARα | Breast cancer ↓ | [77] |
PTEN | Breast cancer ↑ | [198] | ||
PTEN/PI3K/pAkt | CRC ↓ | [199] | ||
PTEN/PI3K/AKT | NSCLC ↓ | [200] | ||
XIAP, caspase 9, caspase 3 | Gastric cancer ↓ | [201] | ||
CTGF, BIRC5, BLC2L1 | Pancreatic cancer ↑ | [202] | ||
MGMT | Glioblastoma ↓ | [203] | ||
SPP1 | HCC ↓ | [204] | ||
SMAD7, TGF-β | Osteosarcoma ↓ | [205] | ||
MiR-193b | CCL2, NTFYα si NRIP1 | DDAH1 | Triple-negative breast cancer ↓ | [206] |
TGF-𝜷, SMAD3, NF1 | CRC, Glioma, Head and neck SCC↑ | [207] | ||
K-Ras, ERBB4 | Lung cancer↓ | [207] | ||
MAX, KRAS, TGF-𝜷, CCND1, ETS1, MAPK | ESCC, Gastric cancer, HCC, Pancreatic cancer ↓ | [207] | ||
Mcl-1, c-kit, MYB | Melanoma, Leukemia ↓ | [207] | ||
caspase 3 and 7, uPA | Ovarian, Prostate cancer ↓ | [207] | ||
miR-210 | NDUFA4 GPD1L | LOXL4 | Lung adenocarcinoma ↑ | [208] |
Glioma ↑ | [209] | |||
Osteosarcoma ↑ | [210] | |||
HOXA 9 | Pancreatic cancer ↑ | [211] | ||
miR-221 | SIRT1 IRS/PI3K/AKT | PTEN/TRAIL | Breast cancer↑ | [212,213] |
ERα, PR, HIF1-α, SLUG | Endometrial cancer↑ | [214] | ||
Prostate cancer ↑ | [98], | |||
MBD2 | OSCC ↑ | [215] | ||
Kit | NSCLC ↑ | [216] | ||
PTEN, PPP2R2A | Osteosarcoma↑ | [217,218] | ||
AKT/ERK pathway | HCC ↑ | [100] | ||
miR-222 | CXCR4 GLUT4 ERs, BTG2, adipor1 | p27 (kip1) | NSLCC | [216] |
MST3 | CRC ↑ | [219] | ||
PPP2R2A | Papillary thyroid cancer ↑ | [220] | ||
miR-221/222 | CAV1 | CAV1 | Breast cancer↑ | [51] |
β4 integrin, STAT5A, and ADAM-17 | Breast cancer↑ | [221] | ||
p27, p57, ER∝ | Breast cancer↑ | [222] | ||
Wnt/β-catenin, WIF1, SFRP2, DKK2, AXIN2 | Breast cancer↑ | [223] | ||
TIMP2 | Gliomas ↑ | [224] | ||
Retinoblastomas ↑ | [225] | |||
miR-302 | Maintain SOX2 and c-Myc by targeting repressor of c-Myc | MACC1 | HCC ↓ | [83] |
Sox2, c-Myc, Nanog | Breast cancer ↑ | [226] | ||
RUNX2 | Breast cancer ↓ | [227] | ||
TGF-β | Mucoepidermoid carcinoma of salivary glands ↑ | [228] | ||
TGFBR2/SMAD3 RAB11A/Wnt/β-Catenin | Pituitary Tumors ↑ | [229] | ||
miR-365 | Cebpα, Fabp4, and Pparγ | BTG2 | Pancreas ↑ | [230] |
ETS1 | NSCLC ↓ | [231] | ||
ADAM1 | Triple negative breast cancer ↓ | [232] | ||
miR-375 | ERK ½ Myotrophin | PSAT1 | ESCC ↓ | [233] |
AEG-1 | HCC, Head and neck cancers ↓ | [234,235] | ||
PDK1, YWHAZ | Gastric ↓ | [236] | ||
miR 3184-3p | FOXP4–NOTCH induced EMT | N-cadherin, vimentin, E-cadherin | Breast cancer ↓ | [77] |
Let 7 | Inhibit HMGA2, inhibit preadipocyte proliferation, insulin-PI3K-mTOR IGF1R, INSR, IRS2 | HMGA2 | Breast cancer ↓ | [302] |
lin-41, hbl-1/lin-57 RAS | Lung cancer ↓ | [229,237,238] | ||
KDM3A/DCLK1/FXYD3 | Lung cancer ↓ | [239] | ||
HGMA2 | Lung cancer ↓ | [240] | ||
RAS, c-MYC | CRC ↑ | [241] | ||
HGMA2 LIN 28 | CRC ↓ | [242,243,244] | ||
E2F2, CCND2 | Prostate cancer↓ | [245] | ||
RAS | Ovarian cancer ↓ | [246] | ||
MYCN | Neuroblastoma ↓ | [247,248] | ||
Aurora-B | Osteosarcoma ↓ | [249] |
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Fodor, A.; Lazar, A.L.; Buchman, C.; Tiperciuc, B.; Orasan, O.H.; Cozma, A. MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis. Int. J. Mol. Sci. 2021, 22, 6337. https://doi.org/10.3390/ijms22126337
Fodor A, Lazar AL, Buchman C, Tiperciuc B, Orasan OH, Cozma A. MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis. International Journal of Molecular Sciences. 2021; 22(12):6337. https://doi.org/10.3390/ijms22126337
Chicago/Turabian StyleFodor, Adriana, Andrada Luciana Lazar, Cristina Buchman, Brandusa Tiperciuc, Olga Hilda Orasan, and Angela Cozma. 2021. "MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis" International Journal of Molecular Sciences 22, no. 12: 6337. https://doi.org/10.3390/ijms22126337