微小RNA-29家族通过调节GEFT功能抑制横纹肌肉瘤的形成和进展。
MicroRNA-29 family inhibits rhabdomyosarcoma formation and progression by regulating GEFT function.
作者信息
Wang Yang, Zhang Liang, Pang Yuweng, Song Lingxie, Shang Hao, Li Zhenzhen, Liu Qianqian, Zhang Yangyang, Wang Xiaomeng, Li Qianru, Zhang Qiaochu, Liu Chunxia, Li Feng
机构信息
Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, The First Affiliated Hospital, Shihezi University School of Medicine Shihezi 832002, China.
Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730, China.
出版信息
Am J Transl Res. 2020 Mar 15;12(3):1136-1154. eCollection 2020.
The microRNA-29 family, which contains mir-29a, mir-29b, and mir-29c, can promote or resist the development of several types of tumors. However, its role in rhabdomyosarcoma (RMS) has not been determined. In this work, we detected the expression of mir-29a/b/c in RMS. Results showed that the tissues and cell lines in RMS were significantly lower than those in muscle and human skeletal muscle cells, and that these cell lines could also inhibit the proliferation, migration, and invasion and induce apoptosis of RMS cells. Dual-luciferase reporter assay and RNA immunoprecipitation verified the direct binding site between mir-29a/b/c and GEFT. Under the combined actions of mir-29a/b/c and GEFT, the former weakened the promoting effect of GEFT on RMS cells. Finally, mir-29a inhibited the tumorigenesis of subcutaneous xenografts in nude mice and inhibited the mRNA and protein expression levels of GEFT in transplanted tumors. These findings proved that mir-29 inhibits the occurrence of RMS and may be a potential molecular target.
包含mir-29a、mir-29b和mir-29c的微小RNA-29家族可促进或抑制多种肿瘤的发展。然而，其在横纹肌肉瘤（RMS）中的作用尚未确定。在本研究中，我们检测了mir-29a/b/c在RMS中的表达。结果显示，RMS中的组织和细胞系显著低于肌肉组织和人骨骼肌细胞中的水平，且这些细胞系还可抑制RMS细胞的增殖、迁移和侵袭并诱导其凋亡。双荧光素酶报告基因检测和RNA免疫沉淀验证了mir-29a/b/c与GEFT之间的直接结合位点。在mir-29a/b/c和GEFT的共同作用下，前者减弱了GEFT对RMS细胞的促进作用。最后，mir-29a抑制了裸鼠皮下异种移植瘤的肿瘤发生，并抑制了移植瘤中GEFT的mRNA和蛋白表达水平。这些发现证明mir-29可抑制RMS的发生，可能是一个潜在的分子靶点。
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