TRMT10C-mediated m7G modification of circFAM126A inhibits lung cancer growth by regulating cellular glycolysis

Abstract

The N⁷-methylguanosine (m7G) modification and circular RNAs (circRNAs) have been shown to play important roles in the development of lung cancer. However, the m7G modification of circRNAs has not been fully elucidated. This study revealed the presence of the m7G modification in circFAM126A. We propose the novel hypothesis that the methyltransferase TRMT10C mediates the m7G modification of circFAM126A and that the stability of m7G-modified circFAM126A is reduced. circFAM126A is downregulated in lung cancer and significantly inhibits lung cancer growth both in vitro and in vivo. The expression of circFAM126A correlates with the stage of lung cancer and with the tumour diameter, and circFAM126A can be used as a potential molecular target for lung cancer. The molecular mechanism by which circFAM126A increases HSP90 ubiquitination and suppresses AKT1 expression to regulate cellular glycolysis, ultimately inhibiting the progression of lung cancer, is elucidated. This study not only broadens the knowledge regarding the expression and regulatory mode of circRNAs but also provides new insights into the molecular mechanisms that regulate tumour cell metabolism and affect tumour cell fate from an epigenetic perspective. These findings will facilitate the development of new strategies for lung cancer prevention and treatment.

Graphical Abstract

Graphical Headlights

• circRNA can undergo m7G modification. The methyltransferase TRMT10C mediates circFAM126A m7G modification, thereby enhancing circFAM126A stability.

• m7G-modified circFAM126A can perform a biological function in inhibiting lung cancer progression by regulating cellular glycolysis.

• circFAM126A increases ubiquitination of HSP90 and inhibits AKT1 expression to regulate cellular glycolysis.