miR18a and miR19a Recruit Specific Proteins for Splicing in Thyroid Cancer Cells

Paiva, Marcelo; Kimura, Edna Teruko; Coltri, Patricia Pereira

doi:10.21873/cgp.20047

Cited by 4 publications

(2 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Third, the local integration of modules promoted by path proliferation and their semi-independence to other modules may provide robustness to mutations on specific proteins, as seen in human cells with SR and hnRNP families of proteins. The hnRNP proteins were previously associated with intronic miRNAs, probably facilitating splicing reactions on these pre-RNA substrates 58 , 59 . Some SR proteins and hnRNP-A2/B1 and hnRNP-U are modulators of splicing in SMN1 and SMN2 genes, but not other hnRNP proteins 60 .…”

Section: Discussionmentioning

confidence: 99%

Interaction paths promote module integration and network-level robustness of spliceosome to cascading effects

Guimarães

Pires

Cantor

et al. 2018

Sci Rep

View full text Add to dashboard Cite

The functionality of distinct types of protein networks depends on the patterns of protein-protein interactions. A problem to solve is understanding the fragility of protein networks to predict system malfunctioning due to mutations and other errors. Spectral graph theory provides tools to understand the structural and dynamical properties of a system based on the mathematical properties of matrices associated with the networks. We combined two of such tools to explore the fragility to cascading effects of the network describing protein interactions within a key macromolecular complex, the spliceosome. Using S. cerevisiae as a model system we show that the spliceosome network has more indirect paths connecting proteins than random networks. Such multiplicity of paths may promote routes to cascading effects to propagate across the network. However, the modular network structure concentrates paths within modules, thus constraining the propagation of such cascading effects, as indicated by analytical results from the spectral graph theory and by numerical simulations of a minimal mathematical model parameterized with the spliceosome network. We hypothesize that the concentration of paths within modules favors robustness of the spliceosome against failure, but may lead to a higher vulnerability of functional subunits, which may affect the temporal assembly of the spliceosome. Our results illustrate the utility of spectral graph theory for identifying fragile spots in biological systems and predicting their implications.

show abstract

Section: Discussionmentioning

confidence: 99%

Interaction paths promote module integration and network-level robustness of spliceosome to cascading effects

Guimarães

Pires

Cantor

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Differential miRNA expression has been reported in PTC vs. normal tissue samples ( 3 – 5 ); certain miRNAs, including serum miR-34a, −155, −197, −221, −224 and −375, can be used as diagnostic and prognostic indicators of thyroid cancer ( 6 , 7 ). The mechanism of action for miR-150, −422a, −18a and −19a in human thyroid cancer has been studied to some extent ( 8 – 10 ); however, there are still a number of miRNAs that may be biologically relevant for the development of thyroid cancer.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR‑486‑5p in papillary thyroid carcinoma tissue: A study based on microarray and miRNA sequencing

et al. 2018

View full text Add to dashboard Cite

Abnormal expression of microRNA (miR) is associated with the occurrence and progression of various types of cancers, including papillary thyroid carcinoma (PTC). In the present study, the aim was to explore miR-486-5p expression and its role in PTC, as well as to investigate the biological function of its potential target genes. The expression levels of miR-486-5p and its clinicopathological significance were examined in 507 PTC and 59 normal thyroid samples via The Cancer Genome Atlas (TCGA). Subsequently, the results were validated using data from Gene Expression Omnibus (GEO) and ArrayExpress. Receiver operating characteristic and summary receiver operating characteristic curves were used to assess the ability of miR-486-5p in distinguishing PTC from normal tissue. Furthermore, potential miR-486-5p mRNA targets were identified using 12 prediction tools and enrichment analysis was performed on the encoding genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The expression levels of miR-486-5p were consistently downregulated in PTC compared with in normal tissue across datasets from TCGA, GEO (GSE40807, GSE62054 and GSE73182) and ArrayExpress (E-MTAB-736). The results also demonstrated that miR-486-5p expression was associated with cancer stage (P=0.003), pathologic lymph node (P=0.047), metastasis (P=0.042), neoplasm (P=0.012) and recurrence (P=0.016) in patients with PTC. In addition, low expression of miR-486-5p in patients with PTC was associated with a worse overall survival. A total of 80 miR-486-5p-related genes were observed from at least 9 of 12 prediction platforms, and these were involved in ‘hsa05200: Pathways in cancer’ and ‘hsa05206: MicroRNAs in cancer’. Finally, three hub genes, CRK like proto-oncogene, phosphatase and tensin homolog and tropomyosin 3, were identified as important candidates in tumorigenesis and progression of PTC. In conclusion, it may be hypothesized that miR-486-5p contributes towards PTC onset and progression, and may act as a clinical target. However, in vitro and in vivo experiments are required to validate the findings of the present study.

show abstract

hnRNP A1 and hnRNP C associate with miR‐17 and miR‐18 in thyroid cancer cells

et al. 2022

View full text Add to dashboard Cite

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are essential players in the regulation of gene expression. The majority of the twenty different hnRNP proteins act through the modulation of pre‐mRNA splicing. Most have been shown to regulate the expression of critical genes for the progression of tumorigenic processes and were also observed to be overexpressed in several types of cancer. Moreover, these proteins were described as essential components for the maturation of some microRNAs (miRNAs). In the human genome, over 70% of miRNAs are transcribed from introns; therefore, we hypothesized that regulatory proteins involved with splicing could be important for their maturation. Increased expression of the miR‐17‐92 cluster has already been shown to be related to the development of many cancers, such as thyroid, lung, and lymphoma. In this article, we show that overexpression of hnRNP A1 and hnRNP C in BCPAP thyroid cancer cells directly affects the expression of miR‐17‐92 miRNAs. Both proteins associate with the 5′‐end of this cluster, strongly precipitate miRNAs miR‐17 and miR‐18a and upregulate the expression of miR‐92a. Upon overexpression of these hnRNPs, BCPAP cells also show increased proliferation, migration, and invasion rates, suggesting upregulation of these proteins and miRNAs is related to an enhanced tumorigenic phenotype.

show abstract

miR18a and miR19a Recruit Specific Proteins for Splicing in Thyroid Cancer Cells

Cited by 4 publications

References 30 publications

Interaction paths promote module integration and network-level robustness of spliceosome to cascading effects

Interaction paths promote module integration and network-level robustness of spliceosome to cascading effects

Downregulation of miR‑486‑5p in papillary thyroid carcinoma tissue: A study based on microarray and miRNA sequencing

hnRNP A1 and hnRNP C associate with miR‐17 and miR‐18 in thyroid cancer cells

Contact Info

Product

Resources

About