Table 1.
The main miRNAs involved in medullary thyroid carcinoma, including gene mechanisms and actions.
| miRNA | Gene Mechanism | Actions |
|---|---|---|
| miR-21 | Upregulates RAS/ERK pathway (targets RASA1 and SPRED1), inhibits PDCD4 and apoptosis | High levels associated with lymph node metastases, advanced stage and postoperative chronic disease; potential therapeutic target [19] |
| miR-375 | Downregulates the PI3K/Akt pathway (targets YAP1, SLC16a2, SEC23A, PARP, JAK2 and NGFR) | Potential biomarker, plasma levels correlate with tumor burden, distant metastasis and response to vandetinib treatment [25] |
| miR-224 | Dysregulates the PI3K/Akt pathway | Low levels in advanced MTC, high levels and positive prognostic factor in sporadic MTC with RAS mutations [31] |
| miR-183 | Inhibits PDCD4 and apoptosis | High levels associated with lateral cervical lymph node metastases, distant metastases and mortality [14,34] |
| miR-127 | Downregulates BAG5 and SEPT7, upregulates Wnt7a |
Low levels in sporadic MTC harboring RET mutation [40] |
| miR-153-3p | Downregulates mTOR pathway (targets RPS6KB1) |
Potential therapeutic effects in combination with tyrosine kinase inhibitors [41] |
| Long-non-coding-RNA—MALAT1 | Downregulates B-MYB, p53, upregulates EMT (targets E-cadherin) | High levels in MTC, in vitro inhibition reduces tumor cell proliferation and invasion [46] |
| miR-31-3p | Downregulates RAS pathway (targets RASA2) |
Low levels in MTC, reduces in vitro MTC cell proliferation [52] |
| miR-34a; miR-144 | Dysregulates PI3K/Akt/mTOR pathway (targets AXL) | High levels in MTC, proposed as biomarkers but lack sufficient specificity and sensitivity [63,64] |
| miR-10a | Downregulates HOXD4 | High levels in primary MTC but downregulated in metastases [15] |
| miR-200 family | Upregulates TGF-β2 (targets ZEB1 and ZEB2) and EMT (targets E-cadherin) | May correlate with metastatic potential [21] |
| miR-323 | Unknown | High levels in MTC but not related to RET mutational status [70] |
| miR-592 | Downregulates FOXO3a and CDK8 | Potential therapeutic target [77] |
| miR-9-3p | Upregulates p21(WAF1/CIP1) and Bcl-XL/Bcl-2 pathway (targets BLCAP) | Enhances cell growth and inhibits apoptosis [16,85] |
| miR-129-5p | Down-regulates the PI3K/Akt pathway (targets RET) | Low level in MTC, acts as tumor suppressor [93] |
| miR-182 | Downregulates FOXO3, MITF, MTSS1, PDCD4 and HES1/Notch1 pathway | Potential blood biomarker for tumor progression [101,102] |
| miR-222-3p; miR-17-5p | Downregulates p27kip1, p57, PTEN, TIMP3 and c-KIT | Potential blood biomarkers [103,104] |