CircSTX6 promotes pancreatic ductal adenocarcinoma progression by sponging miR-449b-5p and interacting with CUL2

• Published in: Molecular cancer 2022-06, Vol.21 (1), p.121-121, Article 121
• Main Authors: Meng, Lingdong, Zhang, Yihan, Wu, Pengfei, Li, Danrui, Lu, Yichao, Shen, Peng, Yang, Taoyue, Shi, Guodong, Chen, Qun, Yuan, Hao, Ge, Wanli, Miao, Yi, Tu, Min, Jiang, Kuirong
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Biotin; Carcinoma, Pancreatic Ductal - pathology; Cell Line, Tumor; Cell proliferation; circSTX6; Cullin; Cullin Proteins - genetics; Development and progression; Exons; Fluorescence in situ hybridization; Gene Expression Regulation, Neoplastic; Genes; Genetic transcription; Genomes; HIF1A; Humans; Hypoxia-inducible factor 1; Hypoxia-inducible factors; Immunoprecipitation; In Situ Hybridization, Fluorescence; Metastases; Metastasis; MicroRNAs - genetics; miR-449b-5p; Muscle proteins; MYH9; Myosin; Pancreas; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; Plasmids; Proteins; Qa-SNARE Proteins; Reverse transcription; Ribonucleic acid; RNA; RNA sequencing; RNA, Circular - genetics; Signal transduction; Therapeutic targets; Tumors; Ubiquitin; Western blotting
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-022-01599-5

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). 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. 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. 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.