scholarly journals MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL

2021 ◽  
Vol 9 ◽  
Author(s):  
Gehao Liang ◽  
Yun Ling ◽  
Qun Lin ◽  
Yu Shi ◽  
Qing Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Biological Function ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Over Expression

ObjectivesCircular RNA (circRNA) is a novel class of RNA, which exhibits powerful biological function in regulating cellular fate of various tumors. Previously, we had demonstrated that over-expression of circRNA circCDYL promoted progression of HER2-negative (HER2–) breast cancer via miR-1275-ULK1/ATG7-autophagic axis. However, the role of circCDYL in HER2-positive (HER2+) breast cancer, in particular its role in modulating cell proliferation, one of the most important characteristics of cellular fate, is unclear.Materials and methodsqRT-PCR and in situ hybridization analyses were performed to examine the expression of circCDYL and miR-92b-3p in breast cancer tissues or cell lines. The biological function of circCDYL and miR-92b-3p were assessed by plate colony formation and cell viability assays and orthotopic animal models. In mechanistic study, circRNAs pull-down, RNA immunoprecipitation, dual luciferase report, western blot, immunohistochemical and immunofluorescence staining assays were performed.ResultsCircCDYL was high-expressed in HER2+ breast cancer tissue, similar with that in HER2– breast cancer tissue. Silencing HER2 gene had no effect on expression of circCDYL in HER2+ breast cancer cells. Over-expression of circCDYL promoted proliferation of HER2+ breast cancer cells but not through miR-1275-ULK1/ATG7-autophagic axis. CircRNA pull down and miRNA deep-sequencing demonstrated the binding of miR-92b-3p and circCDYL. Interestingly, circCDYL did not act as miR-92b-3p sponge, but was degraded in miR-92b-3p-dependent silencing manner. Clinically, expression of circCDYL and miR-92b-3p was associated with clinical outcome of HER2+ breast cancer patients.ConclusionMiR-92b-3p-dependent cleavage of circCDYL was an essential mechanism in regulating cell proliferation of HER2+ breast cancer cells. CircCDYL was proved to be a potential therapeutic target for HER2+ breast cancer, and both circCDYL and miR-92b-3p might be potential biomarkers in predicting clinical outcome of HER2+ breast cancer patients.

mir-556-3p Promotes the Progression of Breast Cancer Through Targeting Disabled Gene Homolog 2 Interacting Protein (DAB2IP)

2021 ◽  
Vol 11 (12) ◽  
pp. 2472-2477
Author(s):  
Chunxiong Fan ◽  
Yanping Deng ◽  
Yaqing Liu ◽  
Xiaoying Liu ◽  
Xi Ke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Activity ◽  
Control Group ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Cancer Pathogenesis

Our study assessed miR-556-3p’s role in breast cancer cells. A total of 65 cases of breast cancer tissue samples were retrospectively analyzed to detect miR-556-3p level by PCR and analyze survival time and 30 normal breast tissues were included as a control group. Breast cancer cells were cultured followed by analysis of cell proliferation by MTT, cell invasion by transwell assay. miR-556-3p level was significantly upregulated in breast cancer patients compared to control group (P <0.05) and inversely associated with survival rate (P <0.05). In vitro experiments, cell activity and invasion were positively correlated with miR-556-3p level (P <0.05). In MCF-7 cell lines, miR-556-3p overexpression increased cell activity (P <0.05). Meanwhile, after miR-556-3p was overexpressed, the expression of DAB2IP, Erk, p-Erk in breast cancer cells was significantly reduced and increased after miR-556-3p was knocked down. In conclusion, miR-556-3p targets DAB2IP3′-UTR, promotes breast cancer cell proliferation, indicating that miR-556-3p might be involved in breast cancer pathogenesis and may be a new target for the treatment.

Cellular Uptake of Soluble Neutrophil Elastase Increases Cyclin E (CCNE) Isoform Expression and Significantly Augments Susceptibility of Breast Cancer Cells to Cytolysis by CCNE-Specific Cytotoxic T Lymphocytes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2090-2090
Author(s):  
Elizabeth Mittendorf ◽  
Gheath Alatrash ◽  
Na Qiao ◽  
Pariya Sukhumalchandra ◽  
Sijie Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Cytotoxic T Lymphocytes ◽  
Breast Cancer Cells ◽  
Inflammatory Cells ◽  
Peripheral Blood Lymphocytes ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Breast Cancer Patients

Abstract Abstract 2090 We have shown that cytotoxic T lymphocytes (CTL) with specificity for the cyclin E (CCNE) derived HLA-A2-restricted peptide CCNE144-152 (ILLDWLMEV) specifically lyse myeloid and lymphoid leukemia in proportion to CCNE overexpression. Full length (FL) CCNE is also overexpressed in most solid tumors, including breast cancer where it is a poor prognostic factor. In addition, leukemia and many breast cancers express tumor-specific low molecular weight (LMW) isoforms of CCNE that result from post-translational processing of the FL protein. Neutrophil elastase (NE), derived from the primary granules of neutrophils, cleaves FL CCNE into LMW forms and NE has been identified in breast cancer tissue. Therefore, we hypothesized that CCNE may also be a breast cancer tumor antigen because the CCNE144-152 peptide is contained within the overexpressed FL and LMW forms, and that effective T cell immunity could be amplified by increased availability of LMW forms within tumor cells exposed to NE. The link between innate immunity, inflammation, and tumor immunity is poorly understood, and this mechanism could explain a role for tumor-infiltrating inflammatory cells in breast cancer. To test this, we elicited CCNE-CTL from peripheral blood lymphocytes of HLA-A2+ healthy donors by weekly stimulation with CCNE-pulsed T2 cells and low-dose IL-2. After 21 days, cytotoxicity of target cells by the lymphocytes was tested with a standard 4-hour calcein AM-based assay. The CCNE-CTL specifically lysed T2 cells pulsed with CCNE (30%) but not non-pulsed T2 cells (0%) at an effector:target (E:T) ratio of 20:1 (p < 0.01). Next, we tested whether CCNE-CTL killed HLA-A2+ MDA-MB-231 (231) breast cancer cells. First, we confirmed that FL CCNE and LMW forms were expressed in 231 cells, while low expression of FL CCNE and no expression of the LMW forms was observed in benign epithelial cells by Western blot. Next, we showed that CCNE-CTL mediated 49% lysis of 231 breast cancer cells at an E:T ratio of 20:1. To look for in vivo evidence of CCNE recognition, we studied peripheral blood lymphocytes from breast cancer patients by flow cytometry with CCNE/HLA-A2 tetramers and anti-CD8 antibodies. In 3 of 4 breast cancer patients we identified CCNE-CTL, with no detectable CCNE-CTL in healthy controls. Together, these results confirm that CCNE is also a tumor antigen in breast cancer. NE, which cleaves CCNE and is expressed in breast cancer tissue, may be produced endogenously by breast cancer cells, or exogenously by inflammatory cells in the tumor microenvironment. Therefore, we studied 231 cells and three other breast cancer cell lines (MDA-MB-453, MCF-7, and HER18) for NE expression. RT-PCR performed with NE-specific primers showed that none of the cells expressed NE mRNA and Western blot showed no NE protein expression, suggesting that NE in tumor tissue derives from neutrophils or other inflammatory cells. To determine whether NE is taken up by breast cancer cells, we used flow cytometry to show that 231 cells pulsed with soluble NE took up an increasing amount of NE and was maximal by 24 hours when intracellular NE expression in 231 cells was comparable to that of HL60 leukemia cells that express high levels of NE. In addition, LMW isoforms of CCNE were increased in NE-pulsed 231 cells, by Western blot. Importantly, CCNE-CTL specific lysis of NE-pulsed 231 cells was 2-fold higher compared to nonpulsed 231 (46% versus 22% at E:T 10:1, p = 0.01). Taken together, these data show that overexpressed CCNE144-152 is a novel breast cancer peptide antigen. Furthermore, exogenous NE is taken up by breast cancer cells, increasing LMW forms of CCNE and enhancing the susceptibility of breast cancer cells to CCNE-CTL-mediated cytolysis. This study links a specific enzyme secreted by neutrophils in the innate immune response to tumors to a specific adaptive immune response against breast cancer, and it suggests that immunotherapy targeting CCNE is warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Signalling mechanisms regulating phenotypic changes in breast cancer cells

2015 ◽  
Vol 35 (2) ◽  
Author(s):  
Natalia Volinsky ◽  
Cormac J. McCarthy ◽  
Alex von Kriegsheim ◽  
Nina Saban ◽  
Mariko Okada-Hatakeyama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Phenotypic Changes ◽  
Model Cell ◽  
Accumulation Of Lipids

Excessive production and accumulation of lipids is often observed in breast cancer tissue. In the current study, we investigate signalling mechanisms regulating this process using a model cell line.

scholarly journals Oleanolic Acid’s Semisynthetic Derivatives HIMOXOL and Br-HIMOLID Show Proautophagic Potential and Inhibit Migration of HER2-Positive Breast Cancer Cells In Vitro

2021 ◽  
Vol 22 (20) ◽  
pp. 11273
Author(s):  
Natalia Magdalena Lisiak ◽  
Izabela Lewicka ◽  
Mariusz Kaczmarek ◽  
Jacek Kujawski ◽  
Barbara Bednarczyk-Cwynar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Cancer Cells ◽  
Oleanolic Acid ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Approximately 20–30% of the diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). This type of cancer is associated with a more aggressive phenotype; thus, there is a need for the discovery of new compounds that would improve the survival in HER2-positive breast cancer patients. It seems that one of the most promising therapeutic cancer strategies could be based on the biological activity of pentacyclic triterpenes’ derivatives and the best-known representative of this group, oleanolic acid (OA). The biological activity of oleanolic acid and its two semisynthetic derivatives, methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL) and 12α-bromo-3-hydroxyimonoolean-28→13-olide (Br-HIMOLID), was assessed in SK-BR-3 breast cancer cells (HER2-positive). Viability tests, cell cycle assessment, evaluation of apoptosis, autophagy, and adhesion/migration processes were performed using MTT, clonogenic, cytofluorometry, Western blot, and qPCR. Both derivatives revealed higher cytotoxicity in studied breast cancer cells than the maternal compound, OA. They also decreased cell viability, induced autophagy, and (when applied in sub-cytotoxic concentrations) decreased the migration of SK-BR-3 cells.This study is the first to report the cytostatic, proautophagic (mTOR/LC3/SQSTM/BECN1 pathway), and anti-migratory (integrin β1/FAK/paxillin pathway) activities of HIMOXOL and Br-HIMOLID in HER2-positive breast cancer cells.

scholarly journals Biological function of long noncoding RNAsnaRin HER2-positive breast cancer cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (6) ◽  
pp. 101042831770737 ◽  
Author(s):  
Jeeyeon Lee ◽  
Ho Yong Park ◽  
Wan Wook Kim ◽  
Soo Jung Lee ◽  
Jae-Hwan Jeong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Biological Function ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals ”BIK/NBK Gene Expression as a Possible Marker of Circulating Breast Cancer Cells in Blood“

2011 ◽  
Vol 4 (1) ◽  
pp. 8-14
Author(s):  
E. Lopez-Munoz ◽  
N. Garcia-Hernandez ◽  
R. I. Penaloza-Espinosa ◽  
M. E. Gomez-Del Toro ◽  
G. Zarco-Espinosa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Breast Cancer Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Mrna Gene

The detection of circulating breast cancer cells in blood could be of special interest as an indicator of diagnosis and prognosis, and for the selection of treatment. In a previous report, our research group determined gene expression profiles in samples of breast cancer tissue, identifying over-expression of the BIK/NBK mRNA gene in 90% of the analyzed samples. In this paper, we analyze the BIK/NBK gene expression as a possible biomarker of circulating breast cancer cells in blood. We demonstrate that the BIK/NBK gene expression is not a significant biomarker in the detection of circulating breast cancer cells in the blood of women with breast cancer. Several studies have evaluated the regulation of apoptosis by estrogens in breast cancer cells, demonstrating the importance of BIK/NBK protein, in estrogen-regulated breast cancer cell apoptosis, which suggests that the regulation of its expression may be an important therapeutic target or strategy in the management of cancer, and, although we did not find statistically significant differences among the patient groups to demonstrate that BIK/NBK gene expression is a biomarker of circulating breast cancer cells in blood, we consider it necessary to continue the study of this gene in breast cancer tissue and its role in the development and progression of breast cancer, its prognostic value, and its potential use as therapeutic target.

scholarly journals miR-200 affects tamoxifen resistance in breast cancer cells through regulation of MYB

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yu Gao ◽  
Wenzhi Zhang ◽  
Chengwen Liu ◽  
Guanghua Li
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tamoxifen Resistance ◽  
Breast Cancer Patients ◽  
Over Expression ◽  
Er Positive ◽  
Emt Markers ◽  
Mcf 7 ◽  
Positive Breast Cancer

AbstractResistance to tamoxifen is a major clinical challenge. Research in recent years has identified epigenetic changes as mediated by dysregulated miRNAs that can possibly play a role in resistance to tamoxifen in breast cancer patients expressing estrogen receptor (ER). We report here elevated levels of EMT markers (vimentin and ZEB1/2) and reduced levels of EMT-regulating miR-200 (miR-200b and miR-200c) in ER-positive breast cancer cells, MCF-7, that were resistant to tamoxifen, in contrast with the naïve parental MCF-7 cells that were sensitive to tamoxifen. Further, we established regulation of c-MYB by miR-200 in our experimental model. C-MYB was up-regulated in tamoxifen resistant cells and its silencing significantly decreased resistance to tamoxifen and the EMT markers. Forced over-expression of miR-200b/c reduced c-MYB whereas reduced expression of miR-200b/c resulted in increased c-MYB We further confirmed the results in other ER-positive breast cancer cells T47D cells where forced over-expression of c-MYB resulted in induction of EMT and significantly increased resistance to tamoxifen. Thus, we identify a novel mechanism of tamoxifen resistance in breast tumor microenvironment that involves miR-200-MYB signaling.

scholarly journals The clinical implication of soluble PD-L1 (sPD-L1) in patients with breast cancer and its biological function in regulating the function of T lymphocyte

2021 ◽  
Author(s):  
Baojuan Han ◽  
Lina Dong ◽  
Jing Zhou ◽  
Yan Yang ◽  
Jiaxun Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
T Lymphocyte ◽  
Breast Cancer Cells ◽  
Biological Function ◽  
Metastatic Breast ◽  
Breast Cancer Patients

AbstractThis work investigated the clinical prognostic implications and biological function of plasma soluble programmed cell death ligand 1 in breast cancer patients. Plasma sPD-L1 levels of recurrent/metastatic breast cancer patients were determined, and the association of sPD-L1 levels and metastatic progression-free survival and metastatic overall survival was assessed. The PD-L1 expression on breast cancer cells was analyzed by flow cytometry, and the level of sPD-L1 in the supernatant of breast cancer cells was determined by enzyme-linked immunosorbent assay. Furthermore, the effect of sPD-L1 on the proliferation and apoptosis of T lymphocytes was detected by WST-1 assay and flow cytometry. The plasma sPD-L1 levels in 208 patients with recurrent/metastatic breast cancer before receiving first-line rescue therapy were measured. The optimal cutoff value of plasma sPD-L1 for predicting disease progression was 8.774 ng/ml. Univariate and multivariate analyses identified high sPD-L1 level (≥ 8.774 ng/ml) and visceral metastasis were independent factors associated with poor prognosis. Relevance analysis showed that the plasma sPD-L1 level was weaklyassociated with some systemic inflammation markers, including white cell count (WBC), absolute monocytecount, and absolute neutrophil count. Furthermore, we found sPD-L1 could be found in supernatant of culture with breast cancer cell line expressing PD-L1 on the cell surface and inhibit T lymphocyte function, playing a negative regulatory role in cellular immunity. sPD-L1 was a good tumor predictive maker in breast cancer and it may play a potentially important role in immune tolerance.

Sign in / Sign up

Export Citation Format

Share Document