Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China.
Clin Transl Med. 2022 Jan;12(1):e707. doi: 10.1002/ctm2.707.
Gastric cancer (GC) ranks third in mortality among all cancers worldwide. Circular RNAs (circRNAs) play an important role in the occurrence and development of gastric cancer. Forkhead box P2 (FOXP2), as a transcription factor, is closely associated with the development of many types of tumours. However, the regulatory network between FOXP2 and circRNAs remains to be explored. In our study, circST3GAL6 was significantly downregulated in GC and was associated with poor prognosis in GC patients. Overexpression of circST3GAL6 inhibited the malignant behaviours of GC cells, which was mediated by inducing apoptosis and autophagy. In addition, we demonstrated that circST3GAL6 regulated FOXP2 through the mir-300 sponge. We further found that FOXP2 inhibited MET Proto-Oncogene (MET), which was the initiating factor that regulated the classic AKT/mTOR pathway of autophagy. In conclusion, our results suggested that circST3GAL6 played a tumour suppressive role in gastric cancer through miR-300/FOXP2 axis and regulated apoptosis and autophagy through FOXP2-mediated transcriptional inhibition of the MET axis, which may become a potential target for GC therapy.
胃癌(GC)在全球所有癌症中死亡率排名第三。环状 RNA(circRNAs)在胃癌的发生和发展中起着重要作用。叉头框 P2(FOXP2)作为一种转录因子,与多种类型肿瘤的发生密切相关。然而,FOXP2 和 circRNAs 之间的调控网络仍有待探索。在我们的研究中,circST3GAL6 在 GC 中显著下调,并与 GC 患者的预后不良相关。circST3GAL6 的过表达抑制了 GC 细胞的恶性行为,这是通过诱导细胞凋亡和自噬来介导的。此外,我们证明 circST3GAL6 通过 mir-300 海绵调控 FOXP2。我们进一步发现,FOXP2 抑制了原癌基因 MET(MET),而 MET 是调节自噬经典 AKT/mTOR 通路的起始因子。总之,我们的研究结果表明,circST3GAL6 通过 miR-300/FOXP2 轴在胃癌中发挥肿瘤抑制作用,并通过 FOXP2 介导的 MET 轴转录抑制调节细胞凋亡和自噬,这可能成为 GC 治疗的潜在靶点。