title: MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP-2 expression.
abstract: Despite the clinical significance of tumorigenesis, little is known about the cellular signaling networks of microRNAs (miRs). Here we report a new finding that mir‑106a regulates the proliferation, migration, and invasion of bladder cancer cells. Basal expression levels of mir‑106a were significantly lower in bladder cancer cells than in normal urothelial cells. Overexpression of mir‑106a suppressed the proliferation of bladder cancer cell line EJ. Transient transfection of mir‑106a into EJ cells led to downregulation of ERK phosphorylation and upregulation of p38 and JNK phosphorylation over their levels in the control. Flow cytometry analysis revealed that mir‑106a-transfected cells accumulated in the G1-phase of the cell cycle, and cyclin D1 and CDK6 were significantly downregulated. This G1-phase cell cycle arrest was due in part to the upregulation of p21CIP1/WAF1. In addition, mir‑106a overexpression blocked the wound-healing migration and invasion of EJ cells. Furthermore, mir‑106a transfection resulted in decreased expression of MMP-2 and diminished binding activity of transcription factor Ets-1 in EJ cells. Collectively, we report the novel mir‑106a-mediated molecular signaling networks that regulate the proliferation, migration, and invasion of bladder cancer cells, suggesting that mir‑106a may be a therapeutic target for treating advanced bladder tumors.
authors: Department of Food Science and Nutrition, Jeju National University, Jeju 63243, Republic of Korea.
authors: Seung-Shick
authors: SS
authors: Shin
authors: Department of Food Science and Nutrition, Jeju National University, Jeju 63243, Republic of Korea.
authors: Sung-Soo
authors: SS
authors: Park
authors: Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors: Byungdoo
authors: B
authors: Hwang
authors: Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors: Won Tae
authors: WT
authors: Kim
authors: Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea.
authors: Yung Hyun
authors: YH
authors: Choi
authors: Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors: Wun-Jae
authors: WJ
authors: Kim
authors: Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors: Sung-Kwon
authors: SK
authors: Moon
mesh_terms: D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D010766:Phosphorylation; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C494041:ETS1 protein, human; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1; D020778:Matrix Metalloproteinase 2