Signaling pathways are complex communication networks that guide how cells function and respond to their environment. They regulate every aspect of cellular function, including growth, division, differentiation, and death. Signaling pathways involve a series of molecular events, including signal reception, amplification, and distribution, as well as the execution of responses.1 microRNAs are key regulators of gene expression and can help regulate signaling pathways.1,2
Disruptions in these signaling pathways, known as dysregulation, can lead to abnormal cellular behavior and contribute to cancer development and progression.3 For example, the PI3K/AKT, MAPK, and Wnt β-catenin pathways represent some of the most common signaling pathways driving thyroid cancer progression and metastasis.4
Understanding the influence of microRNA on signaling pathways is important for understanding how they can be helpful in risk-stratifying indeterminate thyroid nodules.
How microRNAs Influence Signaling Pathways
microRNAs offer valuable insight into gene expression.5 They are master regulators of cellular activity, controlling the types and amounts of proteins made by cells.1 Unlike mRNA, microRNAs do not code for protein themselves; instead, they regulate gene expression at the post-transcriptional level.6,7 Under specific conditions, microRNAs can also activate translation or regulate transcription.1
microRNAs help regulate cellular growth and behavior by controlling protein synthesis and other regulatory functions.5,8,9 Some of their roles that help influence signaling pathways include:
- Engaging in cell-to-cell communication7
- Targeting multiple genes across signaling pathways7
- Exerting their effects without being translated into proteins7
In thyroid cancer, microRNAs have been shown to influence signaling pathways including the MAPK, PI3K/AKT, and RET gene—all of which are associated with tumor growth and progression.2
This helps explain why microRNA analysis represents such a valuable component of molecular testing. Analyzing both mutations and microRNA enables a broader understanding that can help with risk assessment.
Importance of Signaling Pathways in Molecular Testing
The ThyraMIR®v2 panel provides insight into microRNAs that help regulate both major and minor signaling pathways.2 Analyzing these signaling pathways helps provide insight into at least 602 genes–including MAPK (142 genes), PI3K (342 genes), and potentially thousands more through ERK.10-12 This broad level of insight offers a unique advantage and expands understanding beyond a focus solely on mutations.
Signaling Pathways Regulated by microRNAs in ThyraMIRv2 Analysis
| Signaling Pathways* | # of Genes Implicated |
|---|---|
| MAPK | 14210 |
| AKT | 22-300+11,12 |
| PI3K | 34211 |
| JAK/STAT | 1113 |
| DICER 1 | 114 |
| Wnt/β-Catenin | 1915 |
| ERK | Potentially thousands16 |
| Adipocytokine | 3217 |
| TGFβ | 3318 |
The combination of mutational analysis with microRNA signatures in the ThyGeNEXT®+ThyraMIR®v2 testing platform provides an assessment of cellular changes within thyroid nodules. This combined approach helps improve risk stratification for indeterminate thyroid nodules.
microRNA analysis can help support clinical decision-making for indeterminate thyroid nodules.
FAQs
How does ThyGeNEXT+ThyraMIRv2 help improve risk stratification of indeterminate thyroid nodules?
ThyGeNEXT+ThyraMIRv2 is a unique combination testing platform that utilizes an assessment of the most common mutations associated with all types of thyroid carcinoma and microRNA signatures that provide deep insight into the epigenetic regulation of cancer signaling pathways. The assessment of microRNAs with ThyraMIRv2 enables the testing platform to help rule in malignancy, even in the absence of identified mutations by ThyGeNEXT. This dual assessment helps provide a complete picture, improving the risk assessment of indeterminate thyroid nodules from a mutational analysis alone.19,20
How do dysregulated signaling pathways contribute to thyroid cancer development?
How does the ThyraMIRv2 panel evaluate signaling pathways?
The ThyraMIRv2 panel analyzes microRNA signatures. Understanding these signatures provides insight into the regulation of both major and minor signaling pathways involved in thyroid carcinoma.2 This broad level of insight offers a unique advantage and expands understanding beyond a focus solely on mutations.
Patient management decisions are based on the independent medical judgment of the physician and molecular test results should be taken into consideration in conjunction with all relevant imaging, clinical findings, patient and family history, as well as patient preference.
*miR-375, AKT, ERK, PI3K; miR-222, Adipocytokine, JAK/STAT signaling pathway; miR-146b, DICER1 pathway, Wnt/β-Catenin pathway; miR-21, PI3K-AKT; miR-139, MAPK, PI3K; miR-29, TGF-β, Wnt, PI3K-AKT. This listing of microRNA markers is not fully inclusive of all the microRNAs assessed by ThyraMIRv2.
References: 1. O’Brien J, et al. Front Endocrinol (Lausanne). 2018;9:402. doi:10.3389/fendo.2018.00402. 2. Ghafouri-Fard S, et al. Noncoding RNA Res. 2020;5(3):88-98. 3. Infante, D. How Dysregulated Cell Signaling Causes Disease. News-Medical. December 2, 2024. Accessed September 26, 2025. https://www.news-medical.net/health/How-Dysregulated-Cell-Signaling-Causes-Disease.aspx. 4. Zhang J, et al. Cell Death Discov. 2024;10(1):378. 5. Paranjape T, et al. Gut. 2009;58(11):1546-1554. 6. Gulyaeva LF, et al. J Transl Med. 2016;14(1):143. 7. Lee JC, et al. Oncologist. 2014;19(11):1141-1147. 8. What is the “central dogma”? Your Genome. July 21, 2021. Accessed September 26, 2023. https://www.yourgenome.org/facts/what-is-the-central-dogma/. 9. Chen T, et al. Cell Stem Cell. 2015;16(3):289-301. 10. Sinkala M, et al. Commun Biol. 2021;4(1):9. 11. Slattery ML, et al. Mol Carcinog. 2018;57(2):243-261. 12. Catasus L, et al. Mod Pathol. 2010;23(5):694-702. 13. Hu X, et al. Signal Transduct Target Ther. 2021;6(1):402. 14. Vergani-Junior CA, et al. Biophys Rev. 2021;13(6):1081-1090. 15. Driehuis E, et al. Br J Pharmacol. 2017;174(24):4547-4563. 16. Chen JY, et al. Cell Rep. 2023;42(3):112252. 17. Apio C, et al. Front Endocrinol (Lausanne). 2023;14:1165744. 18. Morikawa M, et al. Cold Spring Harb Perspect Biol. 2016;8(5):a021873. 19. Finkelstein SD, et al. Thyroid. 2022;32(11):1362-1371. 20. Lupo MA, et al. Diagn Ctyopathol. 2020;48(12):1254-1264.
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