期刊
MOLECULAR CANCER
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12943-022-01599-5
关键词
Pancreatic ductal adenocarcinoma; circSTX6; miR-449b-5p; HIF1A; MYH9
资金
- National Natural Science Foundation of China [81672449, 81871980]
- National Science Foundation for Young Scientists of China [82103374, 81702447, 81902455]
- Clinical Advanced Technology Program
- Jiangsu Science and Technology Agency [BE2016788]
- Project `333' of Jiangsu Province [BRA2019096]
- Project ` Talents in Medicine' of Jiangsu Province [ZDRCB2016004]
- Project `Six Talent Peaks' of Jiangsu Province [WSW-006]
This study found that circSTX6 promotes the proliferation and metastasis of pancreatic ductal adenocarcinoma cells by regulating the expression of MYH9 through the circSTX6/miR-449b-5p axis and circSTX6/CUL2/HIF1A signaling pathway.
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.
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