CircPSD3 Expression and Its Role in Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) has garnered significant attention due to its rising incidence and the complexities associated with its treatment. Recent studies have indicated that the circular RNA, circPSD3, is notably overexpressed in PTC tissues and is linked to various oncogenic processes (Li et al., 2024). The expression of circPSD3 was found to correlate with tumor progression, suggesting its potential role as a biomarker and therapeutic target. CircRNAs, such as circPSD3, are known for their stability and regulatory functions in cellular processes, including proliferation, migration, and apoptosis (Li et al., 2024).

In an analysis of the GSE93522 dataset, circPSD3 expression was significantly elevated in thyroid cancer tissues compared to adjacent normal tissues. This upregulation suggests that circPSD3 may play a crucial role in the pathogenesis of PTC by promoting cell growth and migration, thereby contributing to tumor aggressiveness and metastasis (Li et al., 2024). Furthermore, the stability of circPSD3, demonstrated through RNase R resistance and prolonged half-life in Act D treatments, reinforces its potential as a therapeutic target in PTC (Li et al., 2024).

Mechanisms of miR-224-5p in Regulating Tumor Progression

The microRNA miR-224-5p has emerged as a key regulator in various malignancies, including non-small cell lung cancer (NSCLC) and PTC. Studies indicate that miR-224-5p expression is frequently downregulated in NSCLC, impacting tumor proliferation and metastasis (Tian et al., 2025). In the context of PTC, miR-224-5p inhibits cell proliferation, migration, and invasion by targeting IL6ST, which is instrumental in activating the JAK2/STAT3 signaling pathway (Tian et al., 2025).

The role of miR-224-5p in modulating the JAK2/STAT3 pathway highlights its potential as a therapeutic target. By inhibiting IL6ST expression, miR-224-5p can suppress the JAK2/STAT3 activation, which is often upregulated in cancer cells, leading to enhanced cell survival and proliferation (Tian et al., 2025). The interplay between miR-224-5p and circPSD3 may provide insights into the molecular mechanisms underlying PTC and offer potential avenues for targeted therapy.

The Impact of BRAF on CircPSD3 and Tumor Development

BRAF mutations, particularly the BRAFV600E mutation, are prevalent in PTC and are associated with aggressive tumor characteristics and poor prognosis (Li et al., 2024). Research suggests that BRAF negatively regulates circPSD3, indicating a potential feedback loop between BRAF signaling and circRNA expression. Elevated BRAF levels lead to the downregulation of circPSD3, which in turn promotes tumor growth and metastasis (Li et al., 2024).

Moreover, the relationship between BRAF and circPSD3 underscores the complex regulatory networks within PTC. The dysregulation of this axis may contribute significantly to tumor advancement, highlighting the importance of targeting both BRAF and circPSD3 in therapeutic strategies (Li et al., 2024). This dual targeting approach could potentially enhance treatment efficacy and improve patient outcomes in PTC.

Functional Assays of CircPSD3 and miR-224-5p in NSCLC

Functional assays have been conducted to elucidate the roles of circPSD3 and miR-224-5p in cancer progression. In vitro studies using cell lines have demonstrated that circPSD3 promotes cell proliferation and migration, while miR-224-5p exhibits growth-inhibitory effects. For instance, transwell assays revealed that silencing circPSD3 led to decreased invasive capabilities of NSCLC cells, while overexpression of miR-224-5p resulted in reduced cell migration and invasion (Tian et al., 2025).

Additionally, xenograft models have shown that the modulation of circPSD3 and miR-224-5p expression significantly impacts tumor growth in vivo. Mice injected with circPSD3-silenced cells exhibited reduced tumor volumes compared to control groups, reaffirming the oncogenic role of circPSD3 in tumorigenesis (Li et al., 2024). These findings collectively underscore the potential of these molecules as therapeutic targets in NSCLC and PTC.

Therapeutic Implications of Targeting CircPSD3 in Cancer Treatment

Given the pivotal roles of circPSD3 and miR-224-5p in tumor progression, targeting these molecules presents a promising therapeutic strategy in PTC and potentially other malignancies. Therapeutic interventions aimed at inhibiting circPSD3 could disrupt its oncogenic signaling pathways, thereby reducing tumor growth and metastasis (Li et al., 2024). Moreover, restoring miR-224-5p expression may provide a mechanism to counteract tumor cell proliferation and invasion by downregulating IL6ST and inhibiting JAK2/STAT3 signaling (Tian et al., 2025).

The development of RNA-based therapeutics, including miRNA mimics and inhibitors, could facilitate the clinical application of these findings. Furthermore, combining circPSD3 targeting with existing treatment modalities such as chemotherapy and immunotherapy may enhance the overall efficacy and provide a more comprehensive approach to managing PTC (Li et al., 2024).

Conclusion

In summary, the interplay between circPSD3 and miR-224-5p plays a critical role in the progression of papillary thyroid carcinoma. CircPSD3 promotes tumor growth and metastasis, while miR-224-5p serves as a negative regulator of IL6ST and JAK2/STAT3 signaling pathways. The regulatory influence of BRAF on circPSD3 expression highlights the complexity of oncogenic signaling in PTC. Targeting these molecules may offer new avenues for therapeutic intervention and improve outcomes for patients with PTC.

References

Li, C., Zhao, X., Zhao, J., An, L., Wu, G. (2024). BRAF regulates circPSD3/miR-526b/RAP2A axis to hinder papillary thyroid carcinoma progression. Journal of Hepatocellular Carcinoma. https://doi.org/10.2147/JHC.S496964
Tian, J., He, Y., Zhang, Z., Zhu, Y., Ren, H. (2025). miR‐224‐5p suppresses non‐small cell lung cancer via IL6ST‐mediated regulation of the JAK2/STAT3 pathway. Thoracic Cancer
Zang, C.-S., Huang, H.-T., Qiu, J., Sun, J., Ge, R.-F. (2020). MiR‐224‐5p targets EGR2 to promote the development of papillary thyroid carcinoma. European Review for Medical and Pharmacological Sciences
Song, Y., et al. (2025). Progress in the Study of Intratumoral Microorganisms in Hepatocellular Carcinoma. Journal of Hepatocellular Carcinoma. https://doi.org/10.2147/JHC.S496964
Wu, Y., et al. (2023). Cuproptosis: molecular mechanisms, cancer prognosis, and therapeutic applications. Journal of Translational Medicine. https://doi.org/10.1186/s12967-025-06121-1

FAQ

What is PTC?

PTC, or papillary thyroid carcinoma, is the most common form of thyroid cancer and is known for its generally favorable prognosis, although some patients may experience aggressive tumor behavior.