Xin Wang1, Chao Li2, Weitao Yao2, Zhichao Tian2, Zhiyong Liu2, Hong Ge3. 1. Department of Bone and Soft Tissue, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China. Electronic address: superwx1984@163.com. 2. Department of Bone and Soft Tissue, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China. 3. Department of Radiation Oncology, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China. Electronic address: gehongzzu@163.com.
Abstract
AIMS: Our previous study has demonstrated that high expression of ALDH1B1 promoted osteosarcoma tumor progression and was correlated with unfavorable prognosis in osteosarcoma patients. In the current study, we investigated the underlying mechanism and regulation of ALDH1B1 in osteosarcoma. MATERIALS AND METHODS: qRT-PCR assay was applied to detect miR-761 expression. CCK-8, colony formation and EdU assays were conducted to explore the functional role of miR-761/ALDH1B1 axis in osteosarcoma. Bioinformatics analysis and luciferase reporter assay was utilized to assess the regulation between miR-761 and ALDH1B1. Mechanism experiments were implemented to investigate the underlying molecular mechanism of miR-761/ALDH1B1 axis. KEY FINDINGS: ALDH1B1 was negatively regulated by microRNA-761 (miR-761). Functionally, miR-761 suppressed cell growth, migration, and invasion in osteosarcoma via targeting ALDH1B1 in vitro. Xenograft tumor model demonstrated that miR-761 inhibited osteosarcoma tumor development in vivo through regulating ALDH1B1. Consistently, we showed that miR-761 expression was decreased in osteosarcoma patients and low expression of miR-761 was correlated with worse prognosis in osteosarcoma patients. Mechanistically, we revealed that high expression of ALDH1B1 was significantly associated with enhanced TGF-β signaling, epithelial-mesenchymal transition (EMT), and cell adhesion. Furthermore, miR-761 regulated TGF-β and EMT/cell adhesion in osteosarcoma via targeting ALDH1B1. SIGNIFICANCE: Taken together, our findings suggest that the oncogenic ALDH1B1 is regulated by miR-761 during osteosarcoma development and progression, which might provide a novel prognostic biomarker and therapeutic strategy for osteosarcoma treatment.
AIMS: Our previous study has demonstrated that high expression of ALDH1B1 promoted osteosarcoma tumor progression and was correlated with unfavorable prognosis in osteosarcomapatients. In the current study, we investigated the underlying mechanism and regulation of ALDH1B1 in osteosarcoma. MATERIALS AND METHODS: qRT-PCR assay was applied to detect miR-761 expression. CCK-8, colony formation and EdU assays were conducted to explore the functional role of miR-761/ALDH1B1 axis in osteosarcoma. Bioinformatics analysis and luciferase reporter assay was utilized to assess the regulation between miR-761 and ALDH1B1. Mechanism experiments were implemented to investigate the underlying molecular mechanism of miR-761/ALDH1B1 axis. KEY FINDINGS:ALDH1B1 was negatively regulated by microRNA-761 (miR-761). Functionally, miR-761 suppressed cell growth, migration, and invasion in osteosarcoma via targeting ALDH1B1 in vitro. Xenograft tumor model demonstrated that miR-761 inhibited osteosarcoma tumor development in vivo through regulating ALDH1B1. Consistently, we showed that miR-761 expression was decreased in osteosarcomapatients and low expression of miR-761 was correlated with worse prognosis in osteosarcomapatients. Mechanistically, we revealed that high expression of ALDH1B1 was significantly associated with enhanced TGF-β signaling, epithelial-mesenchymal transition (EMT), and cell adhesion. Furthermore, miR-761 regulated TGF-β and EMT/cell adhesion in osteosarcoma via targeting ALDH1B1. SIGNIFICANCE: Taken together, our findings suggest that the oncogenic ALDH1B1 is regulated by miR-761 during osteosarcoma development and progression, which might provide a novel prognostic biomarker and therapeutic strategy for osteosarcoma treatment.
Authors: Tao Jiang; Hongyu Wang; Lianyu Liu; Hu Song; Yi Zhang; Jiaqi Wang; Lei Liu; Teng Xu; Ruizhi Fan; Yixin Xu; Shuai Wang; Linsen Shi; Li Zheng; Renhao Wang; Jun Song Journal: Mol Cancer Date: 2021-12-18 Impact factor: 27.401