Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis

Biology Direct

Research

Yanqun Wang¹  Weili Duan²  Xue Kong²  Yao Tong²  Peilong Li²  Juan Li²  Chuanxin Wang²  Xiangjun Dong²  Yafen Wang²  Yanru Li²  Wenjing Zhao³ 

[1] Department of Clinical Laboratory, The 960th Hospital of the PLA Joint Logistics Support Force, 250031, Jinan, Shandong, China;Department of Clinical Laboratory, The Second Hospital of Shandong University, 250033, Jinan, Shandong, China;Pathology Tissue Bank, Qilu Hospital of Shandong University, 250012, Jinan, Shandong, China;

关键词: Breast cancer;    Circular RNA;    HuR;    PD-L1;    Metastasis;    Immune escape;   

DOI  :  10.1186/s13062-023-00397-3

 received in 2023-05-20, accepted in 2023-07-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCircular RNAs (circRNAs) have been shown to play diverse biological functions in the progression of multiple diseases. However, the impacts of circRNAs on breast cancer (BC) progression remains unclear. Therefore, the objective of this paper is to investigate the role and mechanisms of a functional circRNA in BC metastasis and immune escape.MethodsThis study used a circRNA microarray and identified a novel circRNA hsa_circ_0067842. The validation and characteristics of hsa_circ_0067842 were investigated using qRT-PCR, sanger sequencing, RNase R treatment, actinomycin D treatment and fluorescence in situ hybridization (FISH). Gain- and loss-of-function assays were performed to evaluate the biological function of hsa_circ_0067842 in BC progression and immune escape. Mechanistically, the interaction between hsa_circ_0067842 and HuR was explored by RNA pull down, mass spectrometry (MS), subcellular component protein extraction and immunofluorescence (IF). The regulatory mechanisms of hsa_circ_0067842/HuR/CMTM6/PD-L1 axis were investigated by qRT-PCR, western blot, FISH, immunoprecipitation and rescue assays.ResultsThe expression of hsa_circ_0067842 was upregulated in BC tissues and cells, which was found to be significantly associated with poor prognosis, regardless of other clinical covariates. Function assays showed that hsa_circ_0067842 promoted the migration and invasion capacities of BC cells. Moreover, co-culture experiment with peripheral blood mononuclear cells (PBMCs) showed that hsa_circ_0067842 played a role in the immune escape of BC cells. Mechanistically, our study showed that hsa_circ_0067842 interacted with HuR, affecting its nuclear translocation, thus enhancing the stability of CMTM6. CMTM6 not only enhances the migration and invasion ability of BC cells, but also affects the ubiquitination of PD-L1 and inhibits its degradation.ConclusionCollectively, our results demonstrated that hsa_circ_0067842 promoted BC progression through the HuR/CMTM6/PD-L1 axis, providing new insight and a potential target for BC prognosis and therapy.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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