Author:
Cai Feng,Liu Luhua,Bo Yuan,Yan Wenjing,Tao Xuchang,Peng Yuanxiang,Zhang Zhiping,Liao Qi,Yi Yangyan
Abstract
AbstractOsteosarcoma (OS) is a highly malignant tumor, and its dysregulated lipid metabolism is associated with tumorigenesis and unfavorable prognosis. Interestingly, long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of lipid metabolism, exerting notable impacts on tumor proliferation. Nevertheless, the involvement of RPARP-AS1, a novel lipid metabolism-associated lncRNA, remains unexplored in the context of OS. This study aims to identify functionally relevant lncRNAs impacting OS proliferation and lipid metabolism and seeks to shed light on the upstream regulatory mechanisms governing lipogenic enzyme activity. Based on comprehensive bioinformatic analysis and the establishment of a risk model, we identified seven lncRNAs significantly associated with clinical characteristics and lipid metabolism-related genes in patients with OS. Among these, RPARP-AS1 was selected for in-depth investigation regarding its roles in OS proliferation and lipid metabolism. Experimental techniques including RT-qPCR, Western blot, cell viability assay, assessment, and quantification of free fatty acids (FFAs) and triglycerides (TGs) were utilized to elucidate the functional significance of RPARP-AS1 in OS cells and validate its effects on lipid metabolism. Manipulation of RPARP-AS1 expression via ectopic expression or siRNA-mediated knockdown led to alterations in epithelial-mesenchymal transition (EMT) and expression of apoptosis-associated proteins, thereby influencing OS cell proliferation and apoptosis. Mechanistically, RPARP-AS1 was found to augment the expression of key lipogenic enzymes (FABP4, MAGL, and SCD1) and potentially modulate the Akt/mTOR pathway, thereby contributing to lipid metabolism (involving alterations in FFA and TG levels) in OS cells. Collectively, our findings establish RPARP-AS1 as a novel oncogene in OS cells and suggest its role in fostering tumor growth through the enhancement of lipid metabolism.
Funder
The Science and Technology Plan of Health Commission of Jiangxi Province, China
General project of science and technology research of Jiangxi Provincial Department of Education
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference54 articles.
1. Miller BJ, Gao Y, Duchman KR. Socioeconomic measures influence survival in osteosarcoma: an analysis of the National Cancer Data Base. Cancer Epidemiol. 2017;49:112–7.
2. Lettieri CK, Appel N, Labban N, Lussier DM, Blattman JN, Hingorani P. Progress and opportunities for immune therapeutics in osteosarcoma. Immunotherapy. 2016;8:1233–44.
3. Corre I, Verrecchia F, Crenn V, Redini F, Trichet V. The osteosarcoma microenvironment: a complex but targetable ecosystem. Cells. 2020;9:976.
4. Zhu R, Li X, Ma Y. miR-23b-3p suppressing PGC1alpha promotes proliferation through reprogramming metabolism in osteosarcoma. Cell Death Dis. 2019;10:381.
5. Wang X, Hu Z, Wang Z, Cui Y, Cui X. Angiopoietin-like protein 2 is an important facilitator of tumor proliferation, metastasis, angiogenesis and glycolysis in osteosarcoma. Am J Transl Res. 2019;11:6341–55.