Dataset Information

SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness.

ABSTRACT: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with a rapidly increasing incidence globally. Bioinformatics analyses suggested that SHCBP1 (SHC SH2 Domain-Binding Protein 1) was significantly up-regulated in PTC tumor tissues, which was further confirmed by immunohistochemical staining and qPCR analyses in Xuzhou cohort. Moreover, the results indicated that the mRNA level of SHCBP1 was negatively associated with patients' disease-free survival rate, and further analysis reveals that patients with high SHCBP1 expression tend to have more lymph node metastasis. Afterward, MTT, colony formation, cell-cycle assay, FACS apoptosis assay, invasion, migration, as well as scratch assay were performed to study the phenotypes change of PTC cells after knocking down SHCBP1. The in vivo subcutaneous tumor model was developed to study the proliferation ability of PTC cells after SHCBP1 knockdown. We show that knock down of SHCBP1 significantly inhibits PTC cell proliferation, cell cycle, invasion and migration in vivo and in vitro. Western blot and qRT-PCR showed that knockdown of SHCBP1 could significantly reduce MYC, KLF4, CD44, ITGA6, ITGB1, ITGB5, and COL4A2 expression at both RNA and protein levels, which indicated that SHCBP1 might be involved in PTC carcinogenesis and progression through targeting formation of integrin and collagen and cell stemness pathways, and can be a potential diagnosis biomarker and therapeutic target for PTC.

SUBMITTER: Geng H

PROVIDER: S-EPMC7953042 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness.

Geng Houfa H Guo Mengzhe M Xu Wei W Zang Xiu X Wu Tingting T Teng Fei F Wang Yu Y Liu Xuekui X Wang Xiuli X Sun Qiang Q Liang Jun J

Frontiers in endocrinology 20210226

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with a rapidly increasing incidence globally. Bioinformatics analyses suggested that SHCBP1 (SHC SH2 Domain-Binding Protein 1) was significantly up-regulated in PTC tumor tissues, which was further confirmed by immunohistochemical staining and qPCR analyses in Xuzhou cohort. Moreover, the results indicated that the mRNA level of <i>SHCBP1</i> was negatively associated with patients' disease-free survival rate, and further analys ...[more]

PMID: 33716952

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Project description:Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by numerous molecular alterations in addition to previously reported DNA mutations. There is a compelling need to identify novel transcriptomic alterations that are associated with the pathogenesis of PTC with potential diagnostic and prognostic implications. Methods: We gathered and compared 242 expression profiles between paired PTC and adjacent normal tissues and identified and validated the coding and long non-coding RNAs (lncRNAs) associated with the extrathyroidal extension (ETE) of 655 PTC patients in two independent cohorts, followed by predicting their interactions with drugs. Co-expression, RNA interaction, Kaplan-Meier survival and multivariate Cox proportional regression analyses were performed to identify dysregulated lncRNAs and genes that correlated with clinical outcomes of PTC. Alternative splicing (AS), RNA circularization, and editing were also compared between transcriptomes to expand the repertoire of molecular alterations in PTC. Results: Numerous genes related to cellular microenvironment and steroid hormone response were associated with the ETE of PTC. Drug susceptibility predictions of the expression signature revealed two highly ranked compounds, 6-bromoindirubin-3'-oxime and lovastatin. Co-expression and RNA interaction analysis revealed the essential role of lncRNAs in PTC pathogenesis by modulating extracellular matrix and cell adhesion. Eight genes and two novel lncRNAs were identified that correlated with the aggressive nature and disease-free survival of PTC. Furthermore, this study provided the transcriptome-wide landscape of circRNAs in PTC and uncovered dissimilar expression profiles among circRNAs originating from the same host gene, suggesting the functional complexity of circRNAs in PTC carcinogenesis. The newly identified AS events in the SERPINA1 and FN1 genes may improve the sensitivity and specificity of these diagnostic biomarkers. Conclusions: Our study uncovered a comprehensive transcriptomic signature associated with the carcinogenesis and aggressive behavior of PTC, as well as presents a catalog of 10 potential biomarkers, which would facilitate PTC prognosis and development of new therapeutic strategies for this cancer.

Dataset Information

SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness.

Publications

SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness.

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