Background: Natural killer cells play important roles in tumor immune surveillance, and cancer cells must resist this surveillance in order to progress and metastasise.
Introduction: The study aimed to explore the mechanism of how breast cancer cells become resistant to the cytotoxicity of NK cells.
Methods: We established NK-resistant breast cancer cells by exposing MDA-MB-231 cells and MCF-7 cells to NK92 cells. Profiles of lncRNA were compared between the NK-resistant and parental cell lines. Primary NK cells were isolated by MACS, and the NK attacking effect was tested by non-radioactive cytotoxicity. The change in lncRNAs was analyzed by Gene-chip. The interaction between lncRNA and miRNA was displayed by Luciferase assay. The regulation of the gene was verified by QRT-PCR and WB. The clinical indicators were detected by ISH, IH, and ELISA, respectively.
Results: UCA1 was found to be significantly up-regulated in both NK-resistant cell lines, and we confirmed such up-regulation on its own to be sufficient to render parental cell lines resistant to NK92 cells. We found that UCA1 up-regulated ULBP2 via the transcription factor CREB1, while it up-regulated ADAM17 by "sponging" the miR-26b-5p. ADAM17 facilitated the shedding of soluble ULBP2 from the surface of breast cancer cells, rendering them resistant to killing by NK cells. UCA1, ADAM17, and ULBP2 were found to be expressed at higher levels in bone metastases of breast cancer than in primary tumors.
Conclusion: Our data strongly suggest that UCA1 up-regulates ULBP2 expression and shedding, rendering breast cancer cells resistant to killing by NK cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1568009623666230418134253 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterization of stem cell landscape and identification of stemness-relevant prognostic gene signature to aid immunotherapy in breast cancer.
Discov Oncol
January 2025
Department of General Surgery, The Second Affiliated Hospital of the Air Force Medical University, Xi'an, 710038, China.
A common digestive system cancer with a dismal prognosis and a high death rate globally is breast cancer (BRCA). BRCA recurrence, metastasis, and medication resistance are all significantly impacted by cancer stem cells (CSCs). However, the relationship between CSCs and the tumor microenvironment in BRCA individuals remains unknown, and this information is critically needed.
View Article and Find Full Text PDFFrequency of somatic and germline variants of predisposition genes in young Chinese women with breast cancer.
Breast Cancer Res Treat
January 2025
Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian , China.
Purpose: Age stratification influences the clinicopathological features and survival outcomes of breast cancer. We aimed to understand the effect of age on gene variants in young Chinese women with breast cancer compared with those from The Cancer Genome Atlas (TCGA).
Methods: Enrolled patients ≤ 40 years old (N = 370) underwent germline or somatic genetic testing using a 32-gene hereditary cancer panel at Fujian Union Hospital.
Demographic and clinical trends of young breast cancer patients from the national cancer database: disproportionate effect on minority populations.
Breast Cancer Res Treat
January 2025
Division of Medical Oncology, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA.
Purpose: There is an increasing incidence of young breast cancer (YBC) patients with uncertainty surrounding the factors and patterns that are contributing.
Methods: We obtained characteristics and survival data from 206,156 YBC patients (≤ 40 years of age) diagnosed between 2005 and 2019 from the National Cancer Database (NCDB). Patients were subdivided into two comparison groups based on year of diagnosis (2005-2009, Old vs.
Hydrogen Sulfide Promotes TAM-M1 Polarization through Activating IRE-1α Pathway via GRP78 S-Sulfhydrylation to against Breast Cancer.
Adv Sci (Weinh)
January 2025
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, China.
Hydrogen sulfide (HS)-mediated protein S-sulfhydration has been shown to play critical roles in several diseases. Tumor-associated macrophages (TAMs) are the predominant population of immune cells present within solid tumor tissues, and they function to restrict antitumor immunity. However, no previous study has investigated the role of protein S-sulfhydration in TAM reprogramming in breast cancer (BC).
View Article and Find Full Text PDFShort-term Patient-Reported Outcomes Following Bilateral Risk-Reducing Mastectomy for Patients at a High Risk for Breast Cancer: A Systematic Review.
Ann Surg Oncol
January 2025
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Background: Bilateral risk-reducing mastectomies (RRMs) have been proven to decrease the risk of breast cancer in patients at high risk owing to family history or having pathogenic genetic mutations. However, few resources with consolidated data have detailed the patient experience following surgery. This systematic review features patient-reported outcomes for patients with no breast cancer history in the year after their bilateral RRM.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!