CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2
Abstract Background circular RNAs (circRNAs) have been reported to play crucial roles in the biology of different cancers. However, little is known about the function of circSTX6 (hsa_circ_0007905) in pancreatic ductal adenocarcinoma (PDAC). Methods circSTX6, a circRNA containing exons 4, 5, 6 and 7...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-022-01599-5 |
| _version_ | 1811240294113345536 |
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| author | Lingdong Meng Yihan Zhang Pengfei Wu Danrui Li Yichao Lu Peng Shen Taoyue Yang Guodong Shi Qun Chen Hao Yuan Wanli Ge Yi Miao Min Tu Kuirong Jiang |
| author_facet | Lingdong Meng Yihan Zhang Pengfei Wu Danrui Li Yichao Lu Peng Shen Taoyue Yang Guodong Shi Qun Chen Hao Yuan Wanli Ge Yi Miao Min Tu Kuirong Jiang |
| author_sort | Lingdong Meng |
| collection | DOAJ |
| description | Abstract Background circular RNAs (circRNAs) have been reported to play crucial roles in the biology of different cancers. However, little is known about the function of circSTX6 (hsa_circ_0007905) in pancreatic ductal adenocarcinoma (PDAC). Methods circSTX6, a circRNA containing exons 4, 5, 6 and 7 of the STX6 gene, was identified by RNA sequencing and detected by quantitative reverse transcription PCR (qRT–PCR). The biological function of circSTX6 was assessed in vitro and in vivo. The relationship between circSTX6 and miR-449b-5p was confirmed by biotin-coupled circRNA capture, fluorescence in situ hybridization (FISH) and luciferase reporter assays. The interaction of circSTX6 with Cullin 2 (CUL2) was verified by RNA–protein RNA pull-down, RNA immunoprecipitation (RIP) and western blotting assays. Results circSTX6 was frequently upregulated in PDAC tissues, and circSTX6 overexpression promoted tumor proliferation and metastasis both in vitro and in vivo. Furthermore, circSTX6 expression was associated with tumor differentiation and N stage. Mechanistically, circSTX6 regulated the expression of non-muscle myosin heavy chain 9 (MYH9) by sponging miR-449b-5p. Moreover, circSTX6 was confirmed to participate in the ubiquitin-dependent degradation of hypoxia-inducible factor 1-alpha (HIF1A) by interacting with CUL2 and subsequently accelerating the transcription of MYH9. Conclusions Our findings indicate that circSTX6 facilitates proliferation and metastasis of PDAC cells by regulating the expression of MYH9 through the circSTX6/miR-449b-5p axis and circSTX6/CUL2/HIF1A signaling pathway. Therefore, circSTX6 could serve as a potential therapeutic target for the treatment of PDAC. |
| first_indexed | 2024-04-12T13:17:39Z |
| format | Article |
| id | doaj.art-a32c8366eca8404eab160c854ca598de |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-12T13:17:39Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-a32c8366eca8404eab160c854ca598de2022-12-22T03:31:38ZengBMCMolecular Cancer1476-45982022-06-0121112310.1186/s12943-022-01599-5CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2Lingdong Meng0Yihan Zhang1Pengfei Wu2Danrui Li3Yichao Lu4Peng Shen5Taoyue Yang6Guodong Shi7Qun Chen8Hao Yuan9Wanli Ge10Yi Miao11Min Tu12Kuirong Jiang13Pancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityPancreas Center, the First Affiliated Hospital of Nanjing Medical UniversityAbstract Background circular RNAs (circRNAs) have been reported to play crucial roles in the biology of different cancers. However, little is known about the function of circSTX6 (hsa_circ_0007905) in pancreatic ductal adenocarcinoma (PDAC). Methods circSTX6, a circRNA containing exons 4, 5, 6 and 7 of the STX6 gene, was identified by RNA sequencing and detected by quantitative reverse transcription PCR (qRT–PCR). The biological function of circSTX6 was assessed in vitro and in vivo. The relationship between circSTX6 and miR-449b-5p was confirmed by biotin-coupled circRNA capture, fluorescence in situ hybridization (FISH) and luciferase reporter assays. The interaction of circSTX6 with Cullin 2 (CUL2) was verified by RNA–protein RNA pull-down, RNA immunoprecipitation (RIP) and western blotting assays. Results circSTX6 was frequently upregulated in PDAC tissues, and circSTX6 overexpression promoted tumor proliferation and metastasis both in vitro and in vivo. Furthermore, circSTX6 expression was associated with tumor differentiation and N stage. Mechanistically, circSTX6 regulated the expression of non-muscle myosin heavy chain 9 (MYH9) by sponging miR-449b-5p. Moreover, circSTX6 was confirmed to participate in the ubiquitin-dependent degradation of hypoxia-inducible factor 1-alpha (HIF1A) by interacting with CUL2 and subsequently accelerating the transcription of MYH9. Conclusions Our findings indicate that circSTX6 facilitates proliferation and metastasis of PDAC cells by regulating the expression of MYH9 through the circSTX6/miR-449b-5p axis and circSTX6/CUL2/HIF1A signaling pathway. Therefore, circSTX6 could serve as a potential therapeutic target for the treatment of PDAC.https://doi.org/10.1186/s12943-022-01599-5Pancreatic ductal adenocarcinomacircSTX6miR-449b-5pHIF1AMYH9 |
| spellingShingle | Lingdong Meng Yihan Zhang Pengfei Wu Danrui Li Yichao Lu Peng Shen Taoyue Yang Guodong Shi Qun Chen Hao Yuan Wanli Ge Yi Miao Min Tu Kuirong Jiang CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2 Molecular Cancer Pancreatic ductal adenocarcinoma circSTX6 miR-449b-5p HIF1A MYH9 |
| title | CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2 |
| title_full | CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2 |
| title_fullStr | CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2 |
| title_full_unstemmed | CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2 |
| title_short | CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2 |
| title_sort | circstx6 promotes pancreatic ductal adenocarcinoma progression by sponging mir 449b 5p and interacting with cul2 |
| topic | Pancreatic ductal adenocarcinoma circSTX6 miR-449b-5p HIF1A MYH9 |
| url | https://doi.org/10.1186/s12943-022-01599-5 |
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