Activating BRAF mutations have been reported in 40% of papillary thyroid carcinomas (PTCs). The involvement of BRAF pseudogene in thyroid tumorigenesis has not previously been studied. We investigated BRAF pseudogene expression in 68 thyroid tumors: 16 multinodular goiters, 43 classic PTCs, 6 follicular variants of PTC, and 3 anaplastic thyroid carcinomas. BRAF pseudogene function was studied by Western blots, soft agar assay, and tumorigenesis in nude mice. BRAF pseudogene expression was detected in 7 multinodular goiters, 18 classic PTC, and 1 follicular variants of PTC. There is an inverse correlation between BRAF pseudogene expression and BRAF mutation. The pseudogene transcripts were more frequently detected in tumors without BRAF mutation than those with BRAF mutation. Furthermore, BRAF pseudogene expression could activate the MAP kinase signaling pathway, transform NIH3T3 cells in vitro, and induce tumors in nude mice. These data suggest that BRAF pseudogene activation may play a role in thyroid tumor development.
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http://dx.doi.org/10.1593/neo.81044 | DOI Listing |
EXCLI J
November 2024
Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Center, 15 Garbary Street, 61-866 Poznan, Poland.
Cutaneous melanoma is the deadliest form of skin cancer. Despite advancements in treatment, many patients still face poor outcomes. A deeper understanding of the mechanisms involved in melanoma pathogenesis is crucial for improving diagnosis and therapy.
View Article and Find Full Text PDFRep Pract Oncol Radiother
June 2023
Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland.
Background: Skin melanoma is one of the deadliest types of skin cancer and develops from melanocytes. The genetic aberrations in protein-coding genes are well characterized, but little is known about changes in non-coding RNAs (ncRNAs) such as pseudogenes. Ribosomal protein pseudogenes (RPPs) have been described as the largest group of pseudogenes which are dispersed in the human genome.
View Article and Find Full Text PDFSci Rep
May 2021
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
BRAF inhibitors (BRAFi) selectively target oncogenic BRAF and are effective in 80% of advanced cutaneous malignant melanoma cases carrying the V600 mutation. However, the development of drug resistance limits their clinical efficacy. Better characterization of the underlying molecular processes is needed to further improve treatments.
View Article and Find Full Text PDFInt J Cancer
November 2019
Department of Health Sciences, University of Florence, Florence, Italy.
Five-year overall survival of stage III colorectal cancer (CRC) patients treated with standard adjuvant chemotherapy (ACHT) is highly variable. Genomic biomarkers and/or transcriptomic profiles identified lack of adequate validation. Aim of our study was to identify and validate molecular biomarkers predictive of ACHT response in stage III CRC patients by a transcriptomic approach.
View Article and Find Full Text PDFMol Biol Evol
December 2018
Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
The competitive endogenous RNA (ceRNA) hypothesis is an attractively simple model to explain the biological role of many putatively functionless noncoding RNAs. Under this model, there exist transcripts in the cell whose role is to titrate out microRNAs such that the expression level of another target sequence is altered. That it is logistically possible for expression of one microRNA recognition element (MRE)-containing transcript to affect another is seen in the multiple examples of pathogenic effects of inappropriate expression of MRE-containing RNAs.
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