Down-Regulated miR-130a/b Attenuates Rhabdomyosarcoma Proliferation via PPARG

Yi Pan; Junyang Li; Susu Lou; Wanbiao Chen; Yihang Lin; Nan Shen; Youjin Li

doi:10.3389/fmolb.2021.766887

Down-Regulated miR-130a/b Attenuates Rhabdomyosarcoma Proliferation via PPARG

Front Mol Biosci. 2022 Feb 4:8:766887. doi: 10.3389/fmolb.2021.766887. eCollection 2021.

Authors

Yi Pan¹, Junyang Li^{1

2}, Susu Lou¹, Wanbiao Chen^{1

3}, Yihang Lin^{1

2}, Nan Shen^{1

4}, Youjin Li²

Affiliations

¹ Shanghai Children's Medical Center, School of Medicine, Pediatric Translational Medicine Institute, Shanghai Jiao Tong University, Shanghai, China.
² Department of Otolaryngology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Hefei National Laboratory for Physical Sciences at Microscale, The First Affiliated Hospital of USTC, MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China, Hefei, China.
⁴ Department of Infectious Diseases, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Background: 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. Methods: 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. Results: In RMS patients, the expression of miR-130a/b was augmented, and its related PPARG gene was suppressed. Bioinformatics analysis showed that miR-130a/b targeted the PPARG gene and inhibited the proliferation of human RMS cell lines. In addition, rosiglitazone maleate activated the expression of PPARG in human RMS cell lines to suppress proliferation. Conclusion: miR-130a/b regulates the malignant process in RMS by targeting PPARG. Furthermore, the PPARG agonist rosiglitazone maleate attenuated the proliferation of RD cells and might therefore be of benefit to RMS patients.

Keywords: PPARG; miR-130a/b; microRNA; proliferation; rhabdomyosarcoma.