Clinical and functional impact of TARBP2 over-expression in adrenocortical carcinoma
Stefano Caramuta,Linkiat Lee,Deniz M. Ozata,Pinar Akcakaya,Hong Xie,Anders Höög,Jan Zedenius,Martin Bäckdahl,Catharina Larsson,Weng-Onn Lui +9 more
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TLDR
This is the first study to demonstrate the deregulation of miRNA-processing factors in adrenocortical tumors and to show the clinical and biological impact of TARBP2 over-expression in this tumor type.Abstract:
Deregulation of microRNA (miRNA) expression in adrenocortical carcinomas (ACCs) has been documented to have diagnostic, prognostic, as well as functional implications. Here, we evaluated the mRNA expression of DROSHA, DGCR8, DICER (DICER1), TARBP2, and PRKRA, the core components in the miRNA biogenesis pathway, in a cohort of 73 adrenocortical tumors (including 43 adenomas and 30 carcinomas) and nine normal adrenal cortices using a RT-qPCR approach. Our results show a significant over-expression of TARBP2, DICER, and DROSHA in the carcinomas compared with adenomas or adrenal cortices (P<0.001 for all comparisons). Using western blot and immunohistochemistry analyses, we confirmed the higher expression of TARBP2, DICER, and DROSHA at the protein level in carcinoma cases. Furthermore, we demonstrate that mRNA expression of TARBP2, but not DICER or DROSHA, is a strong molecular predictor to discriminate between adenomas and carcinomas. Functionally, we showed that inhibition of TARBP2 expression in human NCI-H295R ACC cells resulted in a decreased cell proliferation and induction of apoptosis. TARBP2 over-expression was not related to gene mutations; however, copy number gain of the TARBP2 gene was observed in 57% of the carcinomas analyzed. In addition, we identified that miR-195 and miR-497 could directly regulate TARBP2 and DICER expression in ACC cells. This is the first study to demonstrate the deregulation of miRNA-processing factors in adrenocortical tumors and to show the clinical and biological impact of TARBP2 over-expression in this tumor type.read more
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Update in Adrenocortical Carcinoma
TL;DR: In advanced ACC, mitotane plus etoposide, doxorubicin, and cisplatin is now the established first-line cytotoxic therapy, however, most patients will experience progress and require salvage therapies, and new treatment concepts are urgently needed.
Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival
Guillaume Assié,Reynies Aurelien de,David S. Rickman,Frédérique Tissier,Lionel Groussin,Fernande René-Corail,Bertrand Dousset,Xavier Bertagna,Eric Clauser,Jérôme Bertherat +9 more
TL;DR: Gene expression analysis unravels two distinct groups of adrenocortical carcinomas and identifies molecular predictors of malignancy and of survival that are reliable and provide valuable independent information in addition to pathology and tumor staging.
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MicroRNA-497 suppresses angiogenesis by targeting vascular endothelial growth factor A through the PI3K/AKT and MAPK/ERK pathways in ovarian cancer.
TL;DR: Findings suggest that downregulation of miR-497 may contribute to angiogenesis in ovarian cancer, and may be a promising candidate target for prevention and treatment of ovarian cancer.
Journal ArticleDOI
The activating TERT promoter mutation C228T is recurrent in subsets of adrenal tumors
Tiantian Liu,Taylor C. Brown,C. Christofer Juhlin,Adam Andreasson,Na Wang,Martin Bäckdahl,James M. Healy,Manju L. Prasad,Reju Korah,Tobias Carling,Dawei Xu,Catharina Larsson +11 more
TL;DR: The TERT promoter mutation C228T is a recurrent event associated with TERT expression in ACCs, but rarely occurs in PGL and PCC, and represents a novel mutated gene in this entity.
Journal ArticleDOI
MicroRNA Machinery Genes as Novel Biomarkers for Cancer.
TL;DR: The preliminary analysis of data from The Cancer Genome Atlas consortium on multiple types of cancer revealed significant alterations in these miRNA machinery genes, and their biological structures and functions are reviewed with an eye toward understanding how they could serve as cancer biomarkers.
References
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