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溶质载体家族25成员10(SLC25A10)在人类骨肉瘤中发挥致癌作用。

SLC25A10 performs an oncogenic role in human osteosarcoma.

作者信息

Wang Gaoyuan, Xia Jianjun, Chen Cheng, Qiu Jie, Sun Po, Peng Zhiwei, Chen Xiaoyu, Xu Bin

机构信息

Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Department of Orthopaedics, East District of The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 231600, P.R. China.

出版信息

Oncol Lett. 2020 Oct;20(4):2. doi: 10.3892/ol.2020.11863. Epub 2020 Jul 14.

Abstract

Osteosarcoma is one of the most common primary malignant bone tumors in adolescents. It is associated with high risk of relapse and the outcomes of patients with high-grade osteosarcoma remain poor. Therefore, additional studies investigating the molecular mechanisms involved in tumor initiation, growth, migration and invasion of osteosarcoma are necessary. In the present study, the protein levels of solute carrier family 25 member 10 (SLC25A10) were increased in osteosarcoma tissue, compared with normal bone tissue. In patients with osteosarcoma, high expression levels of SLC25A10 were associated with poor clinicopathological parameters, including metastasis, clinical Enneking stage, relapse-free survival and overall survival rates. Short hairpin RNA knockdown of SLC25A10 significantly suppressed cell proliferation as determined by cell counting, MTT assay and cell colony formation assays. In addition, SLC25A10 knockdown caused an increase in apoptosis and a decrease in mitosis in osteosarcoma cells. Cyclin E1 (CCNE1) was positively regulated by SLC25A10, while P21 and P27 were negatively regulated by SLC25A10. Therefore, SLC25A10 may play an oncogenic role in human osteosarcoma, which could be mediated by CCNE1, P21 and P27.

摘要

骨肉瘤是青少年最常见的原发性恶性骨肿瘤之一。它与高复发风险相关,高级别骨肉瘤患者的预后仍然很差。因此,有必要进行更多研究来探究骨肉瘤肿瘤起始、生长、迁移和侵袭所涉及的分子机制。在本研究中,与正常骨组织相比,骨肉瘤组织中溶质载体家族25成员10(SLC25A10)的蛋白水平升高。在骨肉瘤患者中,SLC25A10的高表达水平与不良临床病理参数相关,包括转移、临床Enneking分期、无复发生存率和总生存率。通过细胞计数、MTT试验和细胞集落形成试验确定,SLC25A10的短发夹RNA敲低显著抑制了细胞增殖。此外,SLC25A10敲低导致骨肉瘤细胞凋亡增加,有丝分裂减少。细胞周期蛋白E1(CCNE1)受SLC25A10正向调节,而P21和P27受SLC25A10负向调节。因此,SLC25A10可能在人类骨肉瘤中发挥致癌作用,这可能由CCNE1、P21和P27介导。

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