Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Shenzhen University General Hospital, Shenzhen, Guangdong, 518055, China.
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.
Cell Death Dis. 2022 Mar 14;13(3):233. doi: 10.1038/s41419-022-04677-0.
Dysregulation of autophagy and circular RNAs (circRNAs) are involved in the pancreatic cancer (PC) progression. However, the regulatory network between circRNAs, autophagy, and PC progression remains unknown. Herein, we demonstrated that autophagy-associated circRNA circ-autophagy related 7 (circATG7) was elevated in PC tissues compared to adjacent tissues, and in PC cells treated with EBSS and hypoxia. circATG7 expression was positively associated with tumor diameter and lymph node invasion in patients with PC. circATG7 overexpression promoted PC cell proliferation, mobility, and autophagy in vitro, while circATG7 knockdown induced the opposite effects. ATG7 inhibition attenuated the effects of circATG7 on the biological functions of PC cells. CircATG7 is located in the cell cytoplasm and nucleus. Cytoplasmic circATG7 sponged miR-766-5p and decreased its expression, and increased the expression of ATG7, a target gene of miR-766-5p. Nuclear circATG7 acted as a scaffold to increase the interaction between the human antigen R protein and ATG7 mRNA and enhanced ATG mRNA stability. Furthermore, we demonstrated that circATG7 regulates PC cell proliferation and metastasis in vivo via ATG7-dependent autophagy. In conclusion, our results demonstrated that circATG7 accelerates PC progression via miR-766-5p/ATG7 and that HUR/ATG7 depends on autophagic flux. Thus, circATG7 may be a potential therapeutic target for PC.
自噬和环状 RNA（circRNAs）的失调参与了胰腺癌（PC）的进展。然而，circRNAs、自噬与 PC 进展之间的调控网络仍不清楚。在此，我们证明了自噬相关的环状 RNA 环状自噬相关 7（circATG7）在 PC 组织中高于相邻组织，在经 EBSS 和缺氧处理的 PC 细胞中也升高。circATG7 的表达与 PC 患者的肿瘤直径和淋巴结浸润呈正相关。circATG7 过表达促进了 PC 细胞的体外增殖、迁移和自噬，而 circATG7 敲低则诱导了相反的效果。ATG7 抑制减弱了 circATG7 对 PC 细胞生物学功能的影响。circATG7 位于细胞质和细胞核中。细胞质中的 circATG7 可以作为 miR-766-5p 的海绵，降低其表达，同时增加 ATG7 的表达，miR-766-5p 的靶基因。核 circATG7 作为支架，增加了人抗原 R 蛋白与 ATG7 mRNA 之间的相互作用，并增强了 ATG mRNA 的稳定性。此外，我们证明了 circATG7 通过 ATG7 依赖性自噬在体内调节 PC 细胞的增殖和转移。总之，我们的结果表明 circATG7 通过 miR-766-5p/ATG7 加速了 PC 的进展，并且 HUR/ATG7 依赖于自噬流。因此，circATG7 可能是 PC 的一个潜在治疗靶点。
