Project description:Cellular retinoic acid-binding protein 2, encoded by the CRABP2 gene, is a protein that facilitates retinoic acid binding to its cognate receptor complex and transport to the nucleus. Our analysis indicates that CRABP2 expression is upregulated in thyroid cancer and is involved in the invasiveness of thyroid cancer. Loss- and gain-of-function approaches were used to elucidate its oncogenic mechanisms.
Project description:Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous ATC cell lines, and compared their gene expression levels to normal thyroid cell lines.
Project description:Cellular retinoic acid-binding protein 1 (CRABP1) is a cytosolic lipid-binding protein which is thought to play an important role in regulating retinoic acid signaling. Loss of CRABP1 expression has been observed in thyroid cancer. We transfected a CRABP1-overexpressing vector to thyroid cancer cells to elucidate its oncogenic effects.
Project description:The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with very high mortality. Double-stranded RNA–directed RNA interference (dsRNAi) targeting the PIAS2 isoform beta (PIAS2b) inhibits growth of ATC cell lines and patient primary cultures in vitro and orthotopic patient-derived xenografts (oPDX) in vivo, but not of thyroid cell lines or non-anaplastic primary thyroid cultures (differentiated carcinoma, benign lesions, or normal). PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. Strikingly, PIAS2b-dsRNAi induces mitotic catastrophe at prophase. High-throughput proteomics revealed the proteasome (PSMC5) and spindle cytoskeleton as direct targets of PIAS2b SUMOylation at mitotic initiation. PIAS2b-dsRNAi is a promising therapy for ATC and other aggressive anaplastic cancers.
Project description:Anaplastic thyroid carcinoma (ATC) is a rare but deadly thyroid cancer. In contrast, papillary thyroid carcinoma (PTC) is common and highly curable. Minimally invasive biomarkers are needed to distinguish ATC and PTC. Here, by small RNA-seq we show the differential expression levels of several miRNAs, which include miR-34a and miR-210 in ATC compared to PTC cell lines.
Project description:Purpose: The primary goal of this study was to identify gene-expression profiles of anaplastic thyroid cancer and to identify some novel in-frame gene fusions that could result in translated protein products affecting the development of anaplastic thyroid cancer. Methods: RNAseq Data was processed with TCGA UNC V2 RNAseq protocol and different expressed genes were identify by using DESeq2, limma-voom, and edgeR. Potential fusion genes were identified by using SOAPfuse, Chimerascan and TopHat-Fusion. Potential fusion genes were confirmed by cDNA PCR and Sanger sequencing. Results: A total of 21 fusion genes were detected, including six predicted in-frame fusions; none were recurrent. Global gene expression analysis showed 661 genes to be differentially expressed between anaplastic thyroid cancer and papillary thyroid cancer cell lines, with pathway enrichment analyses showing downregulation of TP53-signaling as well as cell adhesion molecules in anaplastic thyroid cancer . Conclusions: Our study represents the first detailed analysis of anaplastic thyroid cancer cell lines and found several novel in-frame gene fusions that could result in translated protein products affecting the development of anaplastic thyroid cancer. These data provide novel insights into the tumorigenesis of anaplastic thyroid cancer and may be used to identify new therapeutic targets.