PMID- 37592296
OWN - NLM
STAT- MEDLINE
DCOM- 20230821
LR  - 20231121
IS  - 1745-6150 (Electronic)
IS  - 1745-6150 (Linking)
VI  - 18
IP  - 1
DP  - 2023 Aug 18
TI  - Circular RNA hsa_circ_0067842 facilitates tumor metastasis and immune escape in 
      breast cancer through HuR/CMTM6/PD-L1 axis.
PG  - 48
LID - 10.1186/s13062-023-00397-3 [doi]
LID - 48
AB  - 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.
CI  - (c) 2023. BioMed Central Ltd., part of Springer Nature.
FAU - Li, Juan
AU  - Li J
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China.
FAU - Dong, Xiangjun
AU  - Dong X
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China.
FAU - Kong, Xue
AU  - Kong X
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China.
FAU - Wang, Yafen
AU  - Wang Y
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China.
FAU - Li, Yanru
AU  - Li Y
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China.
FAU - Tong, Yao
AU  - Tong Y
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China.
FAU - Zhao, Wenjing
AU  - Zhao W
AD  - Pathology Tissue Bank, Qilu Hospital of Shandong University, Jinan, 250012, 
      Shandong, China.
FAU - Duan, Weili
AU  - Duan W
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China.
FAU - Li, Peilong
AU  - Li P
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China. lipeilong@whu.edu.cn.
FAU - Wang, Yanqun
AU  - Wang Y
AD  - Department of Clinical Laboratory, The 960th Hospital of the PLA Joint Logistics 
      Support Force, Jinan, 250031, Shandong, China. wangyan.qun@163.com.
FAU - Wang, Chuanxin
AU  - Wang C
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, 250033, Shandong, China. cxwang@sdu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230818
PL  - England
TA  - Biol Direct
JT  - Biology direct
JID - 101258412
RN  - 0 (B7-H1 Antigen)
RN  - 0 (RNA, Circular)
SB  - IM
MH  - Humans
MH  - B7-H1 Antigen/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Leukocytes, Mononuclear
MH  - *RNA, Circular/genetics
MH  - *Tumor Escape
MH  - *Breast Neoplasms/pathology
MH  - Neoplasm Metastasis
PMC - PMC10436663
OTO - NOTNLM
OT  - Breast cancer
OT  - Circular RNA
OT  - HuR
OT  - Immune escape
OT  - Metastasis
OT  - PD-L1
COIS- The authors declare no competing interests.
EDAT- 2023/08/18 00:42
MHDA- 2023/08/21 06:42
PMCR- 2023/08/18
CRDT- 2023/08/17 23:43
PHST- 2023/05/20 00:00 [received]
PHST- 2023/07/19 00:00 [accepted]
PHST- 2023/08/21 06:42 [medline]
PHST- 2023/08/18 00:42 [pubmed]
PHST- 2023/08/17 23:43 [entrez]
PHST- 2023/08/18 00:00 [pmc-release]
AID - 10.1186/s13062-023-00397-3 [pii]
AID - 397 [pii]
AID - 10.1186/s13062-023-00397-3 [doi]
PST - epublish
SO  - Biol Direct. 2023 Aug 18;18(1):48. doi: 10.1186/s13062-023-00397-3.