Long noncoding RNA AI504432 upregulates FASN expression by sponging miR-1a-3p to promote lipogenesis in senescent adipocytes

Shuwen Wang; Rui Wang; Yaqi Hu; Yifan Zhang; Qi Yuan; Yiyang Luo; Chengfu Yuan

doi:10.1016/j.cellsig.2024.111232

Long noncoding RNA AI504432 upregulates FASN expression by sponging miR-1a-3p to promote lipogenesis in senescent adipocytes

Cell Signal. 2024 May 18:120:111232. doi: 10.1016/j.cellsig.2024.111232. Online ahead of print.

Authors

Shuwen Wang¹, Rui Wang¹, Yaqi Hu¹, Yifan Zhang¹, Qi Yuan², Yiyang Luo², Chengfu Yuan³

Affiliations

¹ Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China; College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
² Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China; College of Medicine and Health Science, China Three Gorges University, Yichang 443002, China.
³ Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China; College of Basic Medical Science, China Three Gorges University, Yichang 443002, China. Electronic address: yuancf46@ctgu.edu.cn.

PMID: 38763183
DOI: 10.1016/j.cellsig.2024.111232

Abstract

Aging affects lipid metabolism and can cause obesity as it is closely related to the disorder of many lipogenic regulatory factors. LncRNAs have been recognized as pivotal regulators across diverse biological processes, but their effects on lipogenesis in aging remain to be further studied. In this work, using RNA sequencing (RNA-Seq), we found that the expression of lncRNA AI504432 was significantly upregulated in the eWAT (epididymal white adipose tissue) of aging mice, and the knockdown of AI504432 notably reduced the expression of several adipogenic genes (e.g., Cebp/α, Srebp-1c, Fasn, Acaca, and Scd1) in senescent adipocytes. The bioinformatics investigation revealed that AI504432 possessed a binding site for miR-1a-3p, and the discovery was verified by the luciferase reporter assay. The expression of Fasn was increased upon the inhibition of miR-1a-3p but restored upon the simultaneous silencing of AI504432. Taken together, our results suggested that AI504432 controlled lipogenesis through the miR-1a-3p/Fasn signaling pathway. The findings may inspire new therapeutic approaches to target imbalanced lipid homeostasis due to aging.

Keywords: Aging; Fasn; Fatty acid synthase; Lipogenesis; LncRNA AI504432; Obesity; Senescence; Sponging; miR-1a-3p.