title: TGF-β1 induces HMGA1 expression: The role of HMGA1 in thyroid cancer proliferation and invasion.
abstract: The role of transforming growth factor-β1 (TGF-β1) is complicated and plays a different role in the development of cancer. High mobility group A (HMGA1) participates in multiple cellular biology processes, and exerts important roles in the epithelial-mesenchymal transition (EMT). However, the correlation of TGF-β1 and HMGA1 in cancer cells is not yet fully understood. In this study, we determined the effects of TGF-β1 on HMGA1 expression in thyroid cancer cells and examined the role of HMGA1 in thyroid cancer progression. With real-time PCR and immunofluorescence staining, our study demonstrated that TGF-β1 induced the expression of HMGA1 through phosphoinositide 3-kinase (PI3K) and the extracellular signal-related kinase (ERK) signaling in thyroid cancer cells. With luciferase reported assay, the HMGA1 promoter activity was activated by TGF-β1 in the SW579 cells. Furthermore, lentivirus-mediated HMGA1 knockdown inhibits cellular oncogenic properties of thyroid cancer cells. Clinically, tissue microarray revealed that HMGA1 was expressed in thyroid carcinoma more than that in normal thyroid tissues (P<0.001); expression of HMGA1 and MMP-2 was identified to be positively correlated (P=0.017). The present study established the first link between HMGA1 and TGF-β1 in the regulation of thyroid cancer proliferation and invasion, and provided evidence for the pivotal role of HMGA1 in the progression of thyroid cancer, indicating HMGA1 to be potential biological marker for the diagnosis of thyroid cancer.
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Shen
authors.affiliation: Department of Metabolism and Endocrinology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Key Laboratory of Tumor Cellular and Molecular Pathology of the College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xu-Yu
authors.initials: XY
authors.lastname: Zu
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Ren-Xian
authors.initials: RX
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025741:HMGA1a Protein / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1; D025741:HMGA1a Protein; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2