Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression

Abstract

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.

Prognostic, Diagnostic, and Clinicopathological Significance of Circular RNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis

“…Another 149 studies were removed for not being related to PC or circRNAs, or not providing sufficient data. Ultimately, a total of 48 papers were included in our meta-analysis, including 34 on prognosis [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ], 11 on diagnosis [ 29 , 30 , 31 , 48 , 55 , 56 , 60 , 61 , 62 , 63 , 64 ], and 30 on relationship with clinicopathological features [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ,…”

Regulation of autophagy fires up the cold tumor microenvironment to improve cancer immunotherapy

“…Hypoxia is the widely accepted stimulator of autophagy induction via HIF-1-mediated expression regulation of key genes associated with autophagy, including adenovirus E1B 19 kDa-interacting protein 3 (BNIP3), BNIP3-like (BNIP3L), ATG9A, PIK3C3, Beclin 1, ATG5 and ATG7 (39)(40)(41)(42)(43). Increased BNIP3 and BNIP3L expression induced by HIF-1, can disrupt the Bcl-2-Beclin1 complex to initiate autophagy (41).…”

“…In addition, hypoxia activates the AMP/AMPK/mTOR pathway and inhibits the PI3K/AKT/mTOR pathway to initiate autophagy ( 44 , 45 ). Through intrinsic cytoprotective pathways, hypoxia-induced autophagy enhances tumor cell survival and contributes to the formation of the immunosuppressive TME that fuels tumor growth ( 39 , 40 , 46 , 47 ). For example, HIF-1-dependent autophagy was crucial in inhibiting CTL and NK cell-mediated anti-tumor immune responses ( 47 , 48 ).…”

Circular RNA-regulated autophagy is involved in cancer progression

“…Subsequent experiments demonstrated that circRHOBTB3 sponged miR-600 to upregulate the NACC1 expression, which further activated the Akt/mTOR pathway to induce cell autophagy. Meanwhile, He et al (2022) discovered upregulation of circATG7 in PDAC tissue, which stabilized autophagy-related 7 (ATG7) mRNA by recruiting HUR and sponging miR-766-5p, a suppressor of ATG7 mRNA, thus increasing the expression of ATG7, which promotes the autophagy process.…”