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MALAT1通过靶向miR-509激活Rac1/JNK通路促进骨肉瘤细胞的增殖和转移。

MALAT1 Promotes the Proliferation and Metastasis of Osteosarcoma Cells By Activating the Rac1/JNK Pathway Via Targeting MiR-509.

作者信息

Zhang Yong, Dai Qingfeng, Zeng Fanying, Liu Haichun

机构信息

Department of Orthopedics, First Hospital of Quanzhou City, Fujian, 362000, China.

Department of Orthopedics, Mudanjiang second People's Hospital, Heilongjiang, 157000, China.

出版信息

Oncol Res. 2018 Apr 27. doi: 10.3727/096504017X14957939026111.

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA (lncRNA) that contributes to the initiation and development of many solid tumors, including osteosarcoma (OS). In this study, we showed that MALAT1 was increased in human OS tissues and cell lines. MALAT1 knockdown suppressed OS cell growth and metastasis, induced OS cell apoptosis and delayed tumor growth in an OS xenograft model. We also detected downregulation of microRNA-509 (miR-509), a suppressor of OS growth, in OS tissues and cell lines. Then, we identified that miR-509 is a direct target of MALAT1 and Ras-related C3 botulinum toxin substrate 1 (Rac1) is a direct target of miR-509. MALAT1 may promote OS cell growth through inhibition of miR-509, leading to the activation of Rac1/JNK pathway. Our results suggest a MALAT1/miR-509/Rac1 axis that mediates OS cell proliferation and tumor progression.

摘要

转移相关的肺腺癌转录本1(MALAT1)是一种长链非编码RNA(lncRNA),它在包括骨肉瘤(OS)在内的许多实体瘤的发生和发展过程中发挥作用。在本研究中,我们发现MALAT1在人骨肉瘤组织和细胞系中表达上调。敲低MALAT1可抑制骨肉瘤细胞的生长和转移,诱导骨肉瘤细胞凋亡,并延缓骨肉瘤异种移植模型中的肿瘤生长。我们还检测到骨肉瘤组织和细胞系中微小RNA-509(miR-509)表达下调,miR-509是一种抑制骨肉瘤生长的因子。随后,我们确定miR-509是MALAT1的直接靶点,而Ras相关的C3肉毒杆菌毒素底物1(Rac1)是miR-509的直接靶点。MALAT1可能通过抑制miR-509促进骨肉瘤细胞生长,从而导致Rac1/JNK通路的激活。我们的研究结果提示了一条介导骨肉瘤细胞增殖和肿瘤进展的MALAT1/miR-509/Rac1轴。

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