Background
Circular RNA UBE2D2 (circ_UBE2D2) has been found to be involved in the progression of breast cancer. Exosomes are critical mediators of intercellular communication, however, the function of exosomal circ_UBE2D2 in breast cancer remains vague.
Material/Methods
Cell viability was measured by Cell Counting Kit-8 assay. Western blot was used to detect the levels of estrogen receptor alpha (ERα), E-cadherin, vimentin, CD9, and CD63. Migrated and invaded cells were examined using Transwell assay. Circ_UBE2D2 and microRNA (miR)-200a-3p levels were detected using quantitative real-time polymerase chain reaction. Exosomes were isolated by ultracentrifugation method. The interaction between circ_UBE2D2 and miR-200a-3p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Murine xenograft model was established to conduct
in vivo
experiments.
Results
We found that circ_UBE2D2 was upregulated in breast cancer tamoxifen-resistant tissues and cell lines, and circ_UBE2D2 deletion mitigated tamoxifen resistance in breast cancer cells. Circ_UBE2D2 was also significantly loaded in exosomes isolated from resistant cells and could be transferred to parental cells. MiR-200a-3p was a target of circ_UBE2D2, and we demonstrated that exosomes mediated transfer of circ_UBE2D2 interacted with miR-200a-3p to enhance tamoxifen resistance of breast cancer cells by regulating cell viability, metastasis, and the level of ERα
in vivo
and
in vitro
.
Conclusions
Exosomes mediated transfer of circ_UBE2D2 reinforced tamoxifen resistance in breast cancer by binding to miR-200a-3p, providing new insights into the boost of the effectiveness of tamoxifen on breast cancer patients.
This article presented a case of a human leukocyte antigen (HLA)-A2-positive patient with advanced cancer/testis antigen New York esophageal squamous cell carcinoma-1 (NY-ESO-1) expressing lung adenocarcinoma (LADC) who received adoptive cell therapy of T cell receptor engineered-T cells (TCR-T cells) targeting the cancer-testis antigen NY-ESO-1. The appropriate clinical and laboratory assessments were conducted to investigate the safety and efficacy of this therapy for this lung cancer patient. The patient had a clinical response to and was well-tolerated with this therapy in the clinical trial. In addition, a preliminary evaluation of the safety of NY-ESO-1 TCR-T cell therapy was performed in four patients with non-small cell lung cancer (NSCLC) enrolled in a clinical trial. It was well-tolerated and did not observe any serious adverse events post-infusion. Fever, anemia, and a decrease in white blood cell count were common adverse events, which were likely due to the TCR-T cell therapy. Two patients had clinical responses to NY-ESO-1 TCR-T cell therapy, including the 44-year-old female patient with LADC, who achieved a short-term partial response for 4 months, improved in Karnofsky performance status, and had a recovery of drug sensitivity. This suggests that TCR-T cell therapy targeting NY-ESO-1 antigen may be beneficial for HLA-A2-positive late-stage patients with NY-ESO-1-expressing NSCLC.
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