Exosomal circSHKBP1 participates in non-small cell lung cancer progression through PKM2-mediated glycolysis

Wenbiao Chen; Donge Tang; Junqi Lin; Xiaoming Huang; Shaoming Lin; Guanle Shen; Yong Dai

doi:10.1016/j.omto.2022.01.012

Exosomal circSHKBP1 participates in non-small cell lung cancer progression through PKM2-mediated glycolysis

Mol Ther Oncolytics. 2022 Feb 2:24:470-485. doi: 10.1016/j.omto.2022.01.012. eCollection 2022 Mar 17.

Authors

Wenbiao Chen¹, Donge Tang², Junqi Lin¹, Xiaoming Huang¹, Shaoming Lin¹, Guanle Shen¹, Yong Dai²

Affiliations

¹ Department of Respiratory Medicine, People's Hospital of Longhua, The Affiliated Hospital of Southern Medical University, Shenzhen 518109, China.
² Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518020, China.

Abstract

Non-small cell lung cancer (NSCLC) has a high morbidity and mortality, and it is imperative to explore the latent pathogenesis mechanism of NSCLC progression to find potential prognostic biomarkers and therapeutic targets. The present study aimed to explore the biological function of circSHKBP1 in NSCLC. circSHKBP1 was found to be upregulated in NSCLC tissues and cell lines and was enriched in exosomes derived from NSCLC cells. Exosomal circSHKBP1 enhanced the proliferation, migration, invasion, and stemness of NSCLC cells. miRNA-1294 was identified as a target for circSHKBP1, and circSHKBP1 upregulated PKM2 expression by sponging miR-1294. Exosomal circSHKBP1 regulated glycolysis through PKM2 in a HIF-1α-dependent manner in NSCLC cells and promoted M2 polarization and macrophage recruitment. Moreover, exosomal circSHKBP1 promoted NSCLC cell growth, metastasis, and M2 infiltration in vivo. Thus, exosomal circSHKBP1 participated in the progression of NSCLC via the miR-1294/PKM2 axis. circSHKBP1 may be potential biomarker for the diagnosis and treatment of NSCLC.

Keywords: circRNA; exosome; glycolysis; macrophage polarization; non-small cell lung cancer.