CircPSD3 Aggravates Tumor Progression by Maintaining TCA Cycle and Mitochondrial Function via Regulating SUCLG2 in Thyroid Carcinoma

Abstract

In recent years, there has been a rapid increase in the incidence of thyroid carcinoma (TC). Our study focuses on the regulatory effect of circular RNAs on metabolism of TC, aiming to provide new insights into the mechanisms of progression and a potential therapeutic target for TC. In this study, we identified high expression levels of circPSD3 in TC tissues through RNA sequencing. Papillary thyroid cancer tissue cohorts verified the circPSD3 expression level was positively correlated with larger tumor size. circPSD3 promoted the proliferation of TC cells and reduced apoptosis both in vitro and vivo. Proteomics and metabolomics suggested that circPSD3 might play a crucial role in regulating the tricarboxylic acid (TCA) cycle. Specifically, circPSD3 acted as a miR-338-5p sponge to upregulate SUCLG2, an enzyme of the TCA cycle, accelerates the conversion of α-ketoglutarate (α-KG) to succinate. Knockdown of circPSD3 disrupts the TCA cycle and impairs mitochondrial function, resulting in decreased membrane potential and aerobic respiration rate. The reduction in mitochondrial function resulted in the inhibition of proliferation and initiation of mitochondria-mediated apoptosis.