title: Silencing of HMGA2 suppresses cellular proliferation, migration, invasion, and epithelial-mesenchymal transition in bladder cancer.
abstract: The high-mobility group protein A2 (HMGA2) is an architectural transcription factor that plays a crucial role in the development and progression of various malignant cancers. However, the function of HMGA2 in bladder cancer remains largely unknown. Therefore, we aim to investigate the effect of HMGA2 on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of bladder cancer cells. The expression of HMGA2 in human bladder cancer cells was downregulated by small interfering RNA (siRNA). The protein levels of HMGA2 and other related proteins were detected by Western blotting. The cell proliferation and apoptosis were examined by Cell Counting Kit-8 and flow cytometry, respectively. Transwell migration and invasion assays were performed to assess the effect of HMGA2 on the migration and invasion ability of cells. In conclusion, we found that HMGA2 knockdown markedly inhibited cell proliferation; this reduced cell growth was due to the high apoptosis rate of cells, as Bcl-xl was diminished, whereas Bax was upregulated. Moreover, our results showed that silencing of HMGA2 in cancer cells greatly inhibited the cell migration and invasion, decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), and affected the occurrence of EMT. We further found that decreased HMGA2 expression suppressed the transforming growth factor-β (TGF-β)/Smad and Wnt/β-catenin signaling pathway in bladder cancer cells. These results revealed that HMGA2 played an important role in the progression of bladder cancer and might be a novel target for therapy in human bladder cancer.
authors.affiliation: Department of Urology, The Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road West, Xuzhou, 221002, Jiangsu Province, People's Republic of China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Urology, The Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road West, Xuzhou, 221002, Jiangsu Province, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, The Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road West, Xuzhou, 221002, Jiangsu Province, People's Republic of China.
authors.forename: Ding
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Urology, The Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road West, Xuzhou, 221002, Jiangsu Province, People's Republic of China.
authors.forename: Run
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Urology, The Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road West, Xuzhou, 221002, Jiangsu Province, People's Republic of China.
authors.forename: Renfu
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Urology, The Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road West, Xuzhou, 221002, Jiangsu Province, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Urology, The Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road West, Xuzhou, 221002, Jiangsu Province, People's Republic of China. sunheyaourology@sina.com.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Sun
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D025743:HMGA2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D025743:HMGA2 Protein; D034741:RNA, Small Interfering
keywords: Bladder cancer; Epithelial–mesenchymal transition; HMGA2; Metastasis; Proliferation