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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04677-0 |
| _version_ | 1828134450364416000 |
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| author | Zhiwei He Kun Cai Zhirui Zeng Shan Lei Wenpeng Cao Xiaowu Li |
| author_facet | Zhiwei He Kun Cai Zhirui Zeng Shan Lei Wenpeng Cao Xiaowu Li |
| author_sort | Zhiwei He |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T17:34:35Z |
| format | Article |
| id | doaj.art-816b8153493e4473970757551aaf58b9 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T17:34:35Z |
| publishDate | 2022-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-816b8153493e4473970757551aaf58b92022-12-22T04:11:39ZengNature Publishing GroupCell Death and Disease2041-48892022-03-0113311510.1038/s41419-022-04677-0Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progressionZhiwei He0Kun Cai1Zhirui Zeng2Shan Lei3Wenpeng Cao4Xiaowu Li5Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Shenzhen University General HospitalGuizhou Medical UniversitySchool of Basic Medicine, Guizhou Medical UniversitySchool of Basic Medicine, Guizhou Medical UniversitySchool of Basic Medicine, Guizhou Medical UniversityDepartment of Hepatobiliary Surgery, Shenzhen Key Laboratory, Shenzhen University General HospitalAbstract 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.https://doi.org/10.1038/s41419-022-04677-0 |
| spellingShingle | Zhiwei He Kun Cai Zhirui Zeng Shan Lei Wenpeng Cao Xiaowu Li Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression Cell Death and Disease |
| title | Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression |
| title_full | Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression |
| title_fullStr | Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression |
| title_full_unstemmed | Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression |
| title_short | Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression |
| title_sort | autophagy associated circrna circatg7 facilitates autophagy and promotes pancreatic cancer progression |
| url | https://doi.org/10.1038/s41419-022-04677-0 |
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