Pan Yi, Li Junyang, Lou Susu, Chen Wanbiao, Lin Yihang, Shen Nan, Li Youjin
Shanghai Children's Medical Center, School of Medicine, Pediatric Translational Medicine Institute, Shanghai Jiao Tong University, Shanghai, China.
Department of Otolaryngology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Mol Biosci. 2022 Feb 4;8:766887. doi: 10.3389/fmolb.2021.766887. eCollection 2021.
Rhabdomyosarcoma (RMS) is one of the most common types of soft-tissue sarcomas in children, and it exhibits a low 5-years survival rate. The survival outcome has shown no significant improvements in the past 30 years miRNA profiling of RMS might therefore provide a novel insight into uncovering new molecular targets for therapy. We analyzed miRNA and RNA sequencing data from patients and the TARGET database to reveal the potential miRNA-mRNA axes and validated them in patients' samples. After the miRNA antagomirs were used to silence the target miRNAs in the cell model, qRT-PCR, western immunoblotting analysis, and proliferation assays were performed to explore the interaction between miR-130a/b and peroxisome proliferator-activated receptor gamma (PPARG) and their effects. In RMS patients, the expression of miR-130a/b was augmented, and its related gene was suppressed. Bioinformatics analysis showed that miR-130a/b targeted the gene and inhibited the proliferation of human RMS cell lines. In addition, rosiglitazone maleate activated the expression of in human RMS cell lines to suppress proliferation. miR-130a/b regulates the malignant process in RMS by targeting . Furthermore, the agonist rosiglitazone maleate attenuated the proliferation of RD cells and might therefore be of benefit to RMS patients.
横纹肌肉瘤（RMS）是儿童最常见的软组织肉瘤类型之一，其5年生存率较低。在过去30年中，RMS的生存结果并无显著改善。因此，RMS的miRNA谱分析可能为揭示新的治疗分子靶点提供新的见解。我们分析了患者的miRNA和RNA测序数据以及TARGET数据库，以揭示潜在的miRNA-mRNA轴，并在患者样本中进行验证。在细胞模型中使用miRNA拮抗剂沉默靶miRNA后，进行qRT-PCR、western免疫印迹分析和增殖试验，以探讨miR-130a/b与过氧化物酶体增殖物激活受体γ（PPARG）之间的相互作用及其影响。在RMS患者中，miR-130a/b的表达增加，其相关基因受到抑制。生物信息学分析表明，miR-130a/b靶向该基因并抑制人RMS细胞系的增殖。此外，马来酸罗格列酮激活人RMS细胞系中该基因的表达以抑制增殖。miR-130a/b通过靶向调节RMS的恶性进程。此外，激动剂马来酸罗格列酮减弱了RD细胞的增殖，因此可能对RMS患者有益。
