MicroRNAs as Potential Biomarkers in Pituitary Adenomas
Abstract
:1. Introduction
2. miRNAs in Non-Functioning PAs
3. miRNAs in Secreting PAs
3.1. miRNAs in Gonadotrophinomas
3.2. miRNAs in Prolactinomas
5. miRNAs Deregulated in a Variety of Pituitary Tumors
5.1. miRNA Expression Profiling in Human Samples from Patients with Pituitary Tumors
5.2. miRNA Expression Profiling in Mouse (AtT-20 and GT1.1) and Rat (GH3 and MMQ) Pituitary Adenoma Cell Lines
5.3. miRNA Expression Profiling in MEN1-Associated Pituitary Adenomas
6. Circulating miRNAs in PAs
7. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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miRNA | Expression Levels | miRNA Profiling Platform | Biological Function | Target Genes | Reference |
---|---|---|---|---|---|
miR-185-5p | ↑ | NGS, qPCR | Status of invasive growth not confirmed by ROC analysis | / 1 | [40] |
miR-137 | ↓ | qPCR | Regulates Wnt signaling pathway | WIF1 | [43] |
miR-370-3p | ↓ | RT-PCR | Increases cell proliferation and invasiveness | HMGA2 | [45] |
miR-145-5p | ↓ | qPCR | Increases cell proliferation and invasiveness | TPT1 | [46] |
miRNA | Expression Levels | miRNA Profiling Platform | Biological Function | Target Genes | Reference |
---|---|---|---|---|---|
miR-145, miR-53, and miR-374 | / 1 | RNA-sequencing | Contribute to tumor development | DEGs 2 mainly enriched in cell cycle and neuroactive ligand-receptor interaction | [47] |
miR-15a, miR-15b, and miR-16 | ↓ | qPCR | Contributes to pituitary tumorigenesis | HMGA1 and HMGA2 | [49] |
miRNA | Expression Levels | miRNA Profiling Platform | Biological Function | Target Genes | Reference |
---|---|---|---|---|---|
miR-7a2 | / 1 | qPCR | Regulates prolactin production | Raf1 | [50] |
miR-93 | ↑ | qPCR | Mediates CAB resistance | ATG7 | [51,52] |
miR-93-5p | ↑ | RNA-sequencing, PCR | Regulates TGF-β1/Smad3 signaling-mediated fibrosis | Smad7 | [53] |
miR-1299 | ↑ | RNA-sequencing, qPCR | Regulates PRL gene transcription participating in the drug resistance | FOXO1 | [54] |
miR-145-5p | ↓ | qPCR | Regulates drug resistance | TPT1 | [55] |
miR-130a-3p | ↓ | Microarray, qPCR | Role in prolactin regulation | ERα | [56] |
miR-137 | ↓ | Microarray, qPCR | Regulates Wnt-β-catenin signaling pathway | MITF | [57] |
miRNA | Expression Levels | miRNA Profiling Platform | Biological Function | Target Genes | Reference |
---|---|---|---|---|---|
Exosomal miR-21-5p | ↑ | qPCR | Regulates osteoblast proliferation, collagen I and osteocalcin synthesis, and bone formation | / 1 | [58] |
miR-34a and miR-145 | ↑ | Microarray, qPCR | Regulates cell proliferation and GH secretion in vitro, but also mediates resistance to the antiproliferative and hormonal properties of octreotide | Gnai2 | [60] |
miR-125b-5p, miR-34a-5p, miR-188-3p, miR-210-5p, miR-27-5p miR-135a-5p, miR-199a-5p miR-211, miR-23a-3p, and miR-204-5p | ↑ ↑ ↑ ↑ ↓ ↓ ↓ ↓ ↓ ↓ | qPCR | Involvement in mesenchymal stem cell commitment | / 1 | [61] |
miR-23b and miR-107 | ↓ | qPCR | / 1 | HMGA2 and AIP | [62] |
let-7c-2, miR-23b, and miR-29c | ↓ | qPCR | Promotes cell proliferation | HMGA, IGF-1, and N-MYC | [63] |
miR-34a | ↓ | qPCR | Promotes cell proliferation and inhibits cell apoptosis | SOX7 | [64] |
miRNA | Expression Levels | miRNA Profiling Platform | Biological Function | Target Genes | Reference |
---|---|---|---|---|---|
miR-449c | ↑ | qPCR | Regulates POMC transcription, ACTH synthesis, cells proliferation, migration, and invasion | TSP-1 | [66] |
miRNA | Expression Levels | miRNA Profiling Platform | Biological Function | Target Genes | Reference |
---|---|---|---|---|---|
miR-181c-5p, and miR-454-3p | / 1 | Microarray, qPCR | Regulate TNFα signaling pathway | / ¹ | [67] |
miR-543 | ↑ | qPCR | Regulates cell proliferation, migration, invasion, apoptosis, and Wnt/β-catenin signaling pathway | Smad7 | [68] |
55 miRNAs | 31 ↑ and 24 ↓ | RNA sequencing | Regulate the invasive behavior | DEGs 2 mainly enriched in cell proliferation and cell cycle pathway | [69] |
miR-410-3p | ↑ or ↓ | qPCR | Regulates MAPK, PTEN/AKT, and STAT3 signaling pathways | / ¹ | [70] |
miR-145, miR-124 and miR-183 | ↓ | Microarray, qPCR | Regulate the migration and invasion | FSCN1, PTTG1IP, and EZR | [71] |
miR-302/372/373/520 | ↓ | qPCR | Regulate cell proliferation, apoptosis, migration, invasion, EMT, and tumor growth | TGFBR2 and RAB11A | [72] |
miR-376B-3P | ↓ | qPCR | Regulates tumor invasiveness | HMGA2 | [73] |
Exosomal miR-99a-3p and miR-149-5p | ↓ | qPCR | Regulate growth and metastasis of pituitary adenoma cells | NOVA1, DTL and RAB27B | [74] |
miR-137 | ↓ | qPCR | Promotes cell proliferation and invasion | AKT2 | [75] |
miR-139-3p | ↓ | qPCR | Promotes cell viability, proliferation, migration, invasion and inhibits apoptosis | BRD4 | [76] |
miR-424-5p | ↓ | qPCR | Promotes cell proliferation, migration, invasion and inhibits apoptosis | bFGF | [77] |
PitNET Types | miRNA | Expression Levels | miRNA Profiling Platform | Biological Function | Target Genes | Reference |
---|---|---|---|---|---|---|
GT 2, CT 3, sCT 4, ST 5 | miR-17-5p | ↑ | qPCR | Involvement in tumor growth and invasiveness | / 1 | [80] |
GH 6, NF 7, PRL 8 | miR-184 miR-34c-3p miR-34b-5p, miR-378, miR-338-5p, miR-124-3p | ↑ ↓ ↓ ↓ ↓ ↓ | NGS, qPCR | / ¹ | / ¹ | [81] |
/ 1 | miR-1 | ↓ | qPCR | Promotes cell proliferation, inhibits cell apoptosis, and glucose metabolism of cancer cells | G6PD | [82] |
GH 6, PRL 8 | miR-205-5p | ↓ | qPCR | Contributes cell proliferation and migration | CBX1 | [87] |
GH 6, PRL 8 | miR-103a-3p | ↓ | qPCR | Promotes rat pituitary adenoma cell proliferation and PI3K/AKT signaling pathway, inhibits cell apoptosis and PRL and GH secretion | / ¹ | [89] |
GT 2, ACTH 9 | miR-219a-2-3p | ↓ | qPCR | Promotes cell proliferation and inhibits cell apoptosis | MDM2 | [90] |
MEN1-related 10 | miR-15a, miR-16, and let-7a | ↓ | qPCR | Regulate CCND1 expression | / ¹ | [92] |
Biological Fluid | miRNA | Expression Levels | miRNA Profiling Platform | Potential Use as Biomarker | Reference |
---|---|---|---|---|---|
Plasma | miR-16-5p, mir-145-5p, and miR-7g-5p | ↑ | qPCR | Distinguishing between CD 1 and EAS 2 patients | [101] |
Plasma | miR-143-3p | ↓ | NGS, qPCR | Patient FSH/LH+ follow up | [102] |
Serum | miR-16 | ↓ | qPCR | Correlation with longer OS 3 and DFS 4 in pituitary tumor patients | [105] |
Serum | miR-423-5p | ↓ | Microarray, NGS, qPCR | Clinical treatment of somatotroph adenomas | [106] |
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Donati, S.; Aurilia, C.; Palmini, G.; Miglietta, F.; Falsetti, I.; Iantomasi, T.; Brandi, M.L. MicroRNAs as Potential Biomarkers in Pituitary Adenomas. Non-Coding RNA 2021, 7, 55. https://doi.org/10.3390/ncrna7030055
Donati S, Aurilia C, Palmini G, Miglietta F, Falsetti I, Iantomasi T, Brandi ML. MicroRNAs as Potential Biomarkers in Pituitary Adenomas. Non-Coding RNA. 2021; 7(3):55. https://doi.org/10.3390/ncrna7030055
Chicago/Turabian StyleDonati, Simone, Cinzia Aurilia, Gaia Palmini, Francesca Miglietta, Irene Falsetti, Teresa Iantomasi, and Maria Luisa Brandi. 2021. "MicroRNAs as Potential Biomarkers in Pituitary Adenomas" Non-Coding RNA 7, no. 3: 55. https://doi.org/10.3390/ncrna7030055