Cargando…
Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis
BACKGROUND: 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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436663/ https://www.ncbi.nlm.nih.gov/pubmed/37592296 http://dx.doi.org/10.1186/s13062-023-00397-3 |
_version_ | 1785092384880590848 |
---|---|
author | Li, Juan Dong, Xiangjun Kong, Xue Wang, Yafen Li, Yanru Tong, Yao Zhao, Wenjing Duan, Weili Li, Peilong Wang, Yanqun Wang, Chuanxin |
author_facet | Li, Juan Dong, Xiangjun Kong, Xue Wang, Yafen Li, Yanru Tong, Yao Zhao, Wenjing Duan, Weili Li, Peilong Wang, Yanqun Wang, Chuanxin |
author_sort | Li, Juan |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00397-3. |
format | Online Article Text |
id | pubmed-10436663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-104366632023-08-19 Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis Li, Juan Dong, Xiangjun Kong, Xue Wang, Yafen Li, Yanru Tong, Yao Zhao, Wenjing Duan, Weili Li, Peilong Wang, Yanqun Wang, Chuanxin Biol Direct Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00397-3. BioMed Central 2023-08-18 /pmc/articles/PMC10436663/ /pubmed/37592296 http://dx.doi.org/10.1186/s13062-023-00397-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Li, Juan Dong, Xiangjun Kong, Xue Wang, Yafen Li, Yanru Tong, Yao Zhao, Wenjing Duan, Weili Li, Peilong Wang, Yanqun Wang, Chuanxin Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis |
title | Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis |
title_full | Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis |
title_fullStr | Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis |
title_full_unstemmed | Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis |
title_short | Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through HuR/CMTM6/PD-L1 axis |
title_sort | circular rna hsa_circ_0067842 facilitates tumor metastasis and immune escape in breast cancer through hur/cmtm6/pd-l1 axis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436663/ https://www.ncbi.nlm.nih.gov/pubmed/37592296 http://dx.doi.org/10.1186/s13062-023-00397-3 |
work_keys_str_mv | AT lijuan circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT dongxiangjun circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT kongxue circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT wangyafen circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT liyanru circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT tongyao circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT zhaowenjing circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT duanweili circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT lipeilong circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT wangyanqun circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis AT wangchuanxin circularrnahsacirc0067842facilitatestumormetastasisandimmuneescapeinbreastcancerthroughhurcmtm6pdl1axis |