Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis.
Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis.
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DOI：
10.1186/s13062-023-00397-3
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发表时间：
2023-08-18
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
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环状RNA（circRNA）已被证明在多种疾病的进展中发挥着多种生物学功能。然而，circRNA 对乳腺癌 (BC) 进展的影响仍不清楚。因此，本文的目的是研究功能性circRNA在BC转移和免疫逃逸中的作用和机制。本研究使用 circRNA 微阵列并鉴定出一种新型 circRNA hsa_circ_0067842。使用 qRT-PCR、桑格测序、RNase R 处理、放线菌素 D 处理和荧光原位杂交 (FISH) 研究 hsa_circ_0067842 的验证和特征。进行功能获得和丧失分析以评估 hsa_circ_0067842 在 BC 进展和免疫逃逸中的生物学功能。从机制上讲，通过 RNA Pull down、质谱 (MS)、亚细胞成分蛋白提取和免疫荧光 (IF) 探索了 hsa_circ_0067842 和 HuR 之间的相互作用。通过 qRT-PCR、蛋白质印迹、FISH、免疫沉淀和救援实验研究了 hsa_circ_0067842/HuR/CMTM6/PD-L1 轴的调节机制。 hsa_circ_0067842 的表达在 BC 组织和细胞中上调，发现与不良预后显着相关，无论其他临床协变量如何。功能检测显示hsa_circ_0067842促进BC细胞的迁移和侵袭能力。此外，与外周血单核细胞（PBMC）的共培养实验表明hsa_circ_0067842在BC细胞的免疫逃逸中发挥作用。从机制上讲，我们的研究表明 hsa_circ_0067842 与 HuR 相互作用，影响其核转位，从而增强 CMTM6 的稳定性。 CMTM6不仅增强BC细胞的迁移和侵袭能力，还影响PD-L1的泛素化并抑制其降解。总的来说，我们的结果表明 hsa_circ_0067842 通过 HuR/CMTM6/PD-L1 轴促进 BC 进展，为 BC 预后和治疗提供了新的见解和潜在目标。在线版本包含可在 10.1186/s13062-023-00397-3 获取的补充材料。
Circular 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. This 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. The 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. Collectively, 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. The online version contains supplementary material available at 10.1186/s13062-023-00397-3.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
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通讯作者：
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影响因子：
16.8
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