CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis

doi:10.1186/s12943-022-01595-9

	CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis
	Hua,Jinghan 1,2,3,5; Wang,Xiaolin 1,5; Ma,Liying 1,5; Li,Jingxin 5; Cao,Guozhen 1,5; Zhang,Shaobo 4; Lin,Wenchu 1,2,3
刊名	Molecular Cancer
	2022-06-06
卷号	21
关键词	CircVAPA SCLC Progression miR-377-3p miR-494-3p IGF1R AKT BMS-536924
DOI	10.1186/s12943-022-01595-9
通讯作者	Lin,Wenchu(wenchu@hmfl.ac.cn)
英文摘要	AbstractBackgroundMultiple lines of evidence have demonstrated that circular RNAs (circRNAs) play oncogenic or tumor-suppressive roles in various human cancers. Nevertheless, the biological functions of circRNAs in small cell lung cancer (SCLC) are still elusive.MethodsCircVAPA (annotated as hsa_circ_0006990) was identified by mining the circRNA profiling dataset of six paired SCLC tissues and the RNA-seq data of serum samples from 36 SCLC patients and 118 healthy controls. The circVAPA expression level was evaluated using quantitative real-time PCR in SCLC cells and tissues. Cell viability, colony formation, cell cycle and apoptosis analysis assays and in vivo tumorigenesis were used to reveal the biological roles of circVAPA. The underlying mechanism of circVAPA was investigated by Western blot, RNA pulldown, RNA immunoprecipitation, dual-luciferase reporter assay and rescue experiments.ResultsWe revealed that circVAPA, derived from exons 2-4 of the vesicle-associated membrane protein-associated protein A (VAPA) gene, exhibited higher expression levels in SCLC cell lines, clinical tissues, and serum from SCLC patients than the controls, and facilitated SCLC progression in vitro and in vivo. Mechanistically, circVAPA activated the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway by modulating the miR-377-3p and miR-494-3p/insulin-like growth factor 1 receptor (IGF1R) axis to accelerate SCLC progression. Furthermore, circVAPA depletion markedly enhanced the inhibitory effects of BMS-536924, an IGF1R kinase inhibitor in cellular and xenograft mouse models.ConclusionsCircVAPA promotes SCLC progression via the miR-377-3p and miR-494-3p/IGF1R/AKT axis. We hope to develop clinical protocols of combinations of circVAPA inhibition and BMS-536924 addition for treating SCLC with circVAPA upregulation.
语种	英语
出版者	BioMed Central
WOS记录号	BMC:10.1186/S12943-022-01595-9
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/129499]
专题	中国科学院合肥物质科学研究院
通讯作者	Lin,Wenchu
作者单位	1.Hefei Institutes of Physical Science, Chinese Academy of Sciences; High Magnetic Field Laboratory 2.Hefei Institutes of Physical Science, Chinese Academy of Sciences; Key Laboratory of High Magnetic Field and Ion Beam Physical Biology 3.High Magnetic Field Laboratory of Anhui Province 4.Anhui Medical University; Department of Pathology and Pathophysiology, School of Basic Medicine 5.University of Science and Technology of China
推荐引用方式 GB/T 7714	Hua,Jinghan,Wang,Xiaolin,Ma,Liying,et al. CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis[J]. Molecular Cancer,2022,21.
APA	Hua,Jinghan.,Wang,Xiaolin.,Ma,Liying.,Li,Jingxin.,Cao,Guozhen.,...&Lin,Wenchu.(2022).CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis.Molecular Cancer,21.
MLA	Hua,Jinghan,et al."CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis".Molecular Cancer 21(2022).