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Review
. 2024 Mar 22;13(7):561.
doi: 10.3390/cells13070561.

Unraveling the Significance of DGCR8 and miRNAs in Thyroid Carcinoma

Lia Rodrigues  1   2   3   4 , Arnaud Da Cruz Paula  1   2 , Paula Soares  1   2   3 , João Vinagre  1   2   3
Affiliations
Review

Unraveling the Significance of DGCR8 and miRNAs in Thyroid Carcinoma

Lia Rodrigues et al. Cells. .

Abstract

MicroRNAs (miRNAs) act as negative regulators for protein-coding gene expression impacting cell proliferation, differentiation, and survival. These miRNAs are frequently dysregulated in cancer and constitute classes of blood-based biomarkers useful for cancer detection and prognosis definition. In thyroid cancer (TC), the miRNA biogenesis pathway plays a pivotal role in thyroid gland formation, ensuring proper follicle development and hormone production. Several alterations in the miRNA biogenesis genes are reported as a causality for miRNA dysregulation. Mutations in microprocessor component genes are linked to an increased risk of developing TC; in particular, a recurrent mutation affecting DGCR8, the E518K. In this review, we explore these novel findings and resume the current state-of-the-art in miRNAs in thyroid carcinomas.

Keywords: DGCR8; E518K; microRNAs; thyroid cancer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
miRNA biogenesis pathway: miRNA genes are transcribed into the nucleus by RNA pol II into primary structures—pri-miRNA. The microprocessor complex composed of DROSHA and its binding partner DGCR8 cleaves the pri-miRNA into a hairpin pre-miRNA structure. The pre-miRNAs are then exported to cytoplasm by XPO5 where DICER processes the pre-miRNA into mature miRNA. The mature form is incorporated into RISC which will guide the mature miRNA to target mRNAs, regulating gene expression post-transcriptionally by mRNA degradation or translational repression. The figure was created with BioRender.com.
Figure 2
Figure 2
Schematic representation of the balance between oncogenic miRNAs and tumor-suppressor miRNAs. Downregulation of tumor-suppressor miRNAs could result in overexpression of oncogene mRNAs by reducing degradation. In turn, overexpression of oncogenic miRNAs could result in the downregulation of tumor-suppressor gene mRNAs by increasing mRNA degradation. Both processes have an impact on hallmarks of cancer such as cell proliferation, immortalization, and angioinvasion. The figure was created with BioRender.com.
Figure 3
Figure 3
miRNA overexpression (red) and downregulation (green) are able to distinguish tumoral and non-tumoral counterpart tissues and different histotype stratification in TC. Regarding PTC, miR-146 is commonly found upregulated. In FTC, an upregulation of miR-192, -197, -328, and -348 is described when compared to the normal counterpart. PDTC and ATC, which are more likely to metastasize (depicted by the arrow), also present specific miRNAs up- and downregulated, that being the downregulation of miR-200 and miR-30 families strongly associated with ATC. PTC: papillary thyroid carcinoma; FTC: follicular thyroid carcinoma; PDTC: poorly differentiated thyroid carcinoma; ATC: anaplastic thyroid carcinoma. The figure was created with BioRender.com.
See this image and copyright information in PMC

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