GC-MSC-derived circ_0024107 promotes gastric cancer cell lymphatic metastasis via fatty acid oxidation metabolic reprogramming mediated by the miR-5572/6855-5p/CPT1A axis

Gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) play a critical role in facilitating gastric cancer metastasis. Recently, circular RNAs (circRNAs) and metabolic reprogramming have been found to be extensively involved in the malignant progression of tumors, including gastric cancer. However, the biological role and potential mechanisms of GC-MSC-derived circRNAs in metabolic reprogramming remain elusive. Herein, the expression profiles of circRNAs and mRNAs were compared between GC-MSCs and bone marrow-derived MSCs (BM-MSCs) using microarray analysis. circ_0024107 was identified to mediate GC-MSCs to promote gastric cancer lymphatic metastasis by inducing fatty acid oxidation (FAO) metabolic reprogramming. Mechanistically, circ_0024107 served as a sponge of miR-5572 and miR-6855-5p to elicit the FAO metabolic reprograming of GC-MSCs by upregulating carnitine palmitoyltransferase 1A (CPT1A). In addition, GC-MSCs promoted metastasis which was dependent on the induction of FAO in gastric cancer cells mediated by circ_0024107. The circ_0024107/miR-5572/6855-5p/CPT1A axis was deregulated in gastric cancer tissues and GC-MSCs, and was associated with lymph node metastasis and the prognosis of patients with gastric cancer. Taken together, the findings of the present study suggest the crucial role of FAO metabolic reprogramming mediated by GC-MSC-derived circ_0024107 in synergistically promoting gastric cancer lymphatic metastasis via miR-5572/6855-5p-CPT1A signaling; this suggests that circ_0024107 may be an attractive target for gastric cancer intervention.

Automated summary

In this study, it was found that gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) play a critical role in promoting gastric cancer metastasis. The researchers also discovered the involvement of circular RNAs (circRNAs) and metabolic reprogramming in the malignant progression of gastric cancer. Specifically, circ_0024107 was identified as a mediator of GC-MSCs promoting gastric cancer lymphatic metastasis by inducing fatty acid oxidation (FAO) metabolic reprogramming. Mechanistically, circ_0024107 acted as a sponge for miR-5572 and miR-6855-5p, thereby upregulating carnitine palmitoyltransferase 1A (CPT1A) to induce FAO metabolic reprogramming in GC-MSCs.