Dataset Information

Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion.

ABSTRACT: Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined, limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison with the central regions of primary PTCs, the invasive fronts overexpressed TGF beta, NFkappaB and integrin pathway members, and regulators of small G proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 34 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required both for the development and maintenance of a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is common in PTC invasion and that vimentin regulates thyroid cancer EMT in vitro.

SUBMITTER: Vasko V

PROVIDER: S-EPMC1815262 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion.

Vasko Vasily V Espinosa Allan V AV Scouten William W He Huiling H Auer Herbert H Liyanarachchi Sandya S Larin Alexander A Savchenko Victoria V Francis Gary L GL de la Chapelle Albert A Saji Motoyasu M Ringel Matthew D MD

Proceedings of the National Academy of Sciences of the United States of America 20070212 8

Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined, limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed ...[more]

PMID: 17296934

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Project description:Background: Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignant tumors. Poor prognoses such as high recurrence rate always appear in PTC patients with cervical lymph node metastasis. The process of ubiquitination plays important roles in PTC. As ubiquitin E3 ligases, Deltex (DTX) family proteins were reported to associate with multiple cancers. However, functions and mechanisms of DTX3 in PTC are currently unknown. Methods: In this study, DTX3 expressions were examined in 114 PTC and paired paracancerous normal tissues through quantitative real-time polymerase chain reaction and western blot. The clinical significances of DTX3 expressions in PTC patients were also investigated. After stable transfection with either short hairpin RNA to knock down DTX3 expression or full-length complementary DNA to upregulate DTX3 expression, changes of malignant phenotypes in two PTC cell lines K1 and TPC-1 were observed using cell viability, flow cytometry, wound healing and transwell assays. Afterwards, altered expressions of epithelial-mesenchymal transition (EMT) and AKT signal pathway related proteins were measured by western blot. Immunoprecipitation and mass spectrometry (IP-MS), immunofluorescence and Co-IP were utilized to identify the possible DTX3 interacting proteins. Results: Both mRNA and protein expressions of DTX3 were lower in PTC tissues and correlated with the presence of cervical lymph node metastasis (P<0.05). DTX3 overexpression inhibited migration and invasion of PTC cells, decreased Vimentin and phosphorylated AKT expressions, but promoted E-cadherin expression (P<0.05). Moreover, knockdown of DTX3 led to opposite changes (P<0.05). Total 46 probable DTX3 interacting proteins were identified by IP-MS. Among them, X-ray repair cross-complementing protein 5 (XRCC5) and NADH: Ubiquinone Oxidoreductase Complex Assembly Factor 5 (NDUFAF5) were verified to be associated with DTX3. Moreover, DTX3 was proved to be co-localized with XRCC5 in nucleus and promote ubiquitination of XRCC5. Conclusions: DTX3 suppresses EMT by partially facilitating ubiquitination of XRCC5 to inhibit AKT signal pathway in PTC.

Project description:Thyroid carcinoma (THCA) is a common type of endocrine system cancer and its current clinical treatment method is surgical resection. Long non‑coding RNAs (lncRNAs) have been revealed to serve important roles in a variety of complex human diseases. Therefore, determining the association between lncRNAs and diseases may provide novel insight into disease‑related lncRNAs, with the aim of improving disease treatments and diagnoses. Long intergenic non‑protein coding RNA 1816 (LINC01816) was identified to be associated with the survival of patients with colorectal cancer using the IDHI‑MIRW method. The present study aimed to investigate the role and molecular mechanism of LINC01816 in THCA. Analysis of datasets from The Cancer Genome Atlas database revealed that the upregulation of LINC01816 expression levels was associated with a variety of cancer types. Reverse transcription‑quantitative PCR analysis demonstrated that compared with the normal thyroid tissues, the expression levels of LINC01816 were upregulated in THCA tissues. The results of wound healing and Transwell assays, and western blotting demonstrated that the overexpression of LINC01816 could strengthen the invasive and migratory abilities of THCA cells and enhance epithelial‑mesenchymal transition progression. Analysis using the starBase website and dual‑luciferase reporter assays identified that microRNA (miR)‑34c‑5p was a target of LINC01816. The overexpression of miR‑34c‑5p could inhibit the invasive and migratory abilities of THCA cells, in addition to inhibiting the cellular retinoic acid binding protein 2 (CRABP2) overexpression‑induced effects on invasion, migration and EMT processes. In conclusion, the findings of the present study indicated that LINC01816 may be capable of sponging miR‑34c‑5p to upregulate CRABP2 expression levels, which subsequently promoted the invasion, migration and EMT of THCA cells. Therefore, targeting the LINC01816/miR‑34c‑5p/CRABP2 pathway may be an effective therapeutic approach for patients with THCA.

Dataset Information

Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion.

Publications

Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion.

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