TRAF2 regulates the cytoplasmic/nuclear distribution of TRAF4 and its biological function in breast cancer cells

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.

Download Full-text

MiR-346 promotes the biological function of breast cancer cells by targeting SRCIN1 and reduces chemosensitivity to docetaxel

Gene ◽

10.1016/j.gene.2016.11.037 ◽

2017 ◽

Vol 600 ◽

pp. 21-28 ◽

Cited By ~ 23

Author(s):

Fan Yang ◽

Long-ji Luo ◽

Lei Zhang ◽

Dan-dan Wang ◽

Su-jin Yang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Biological Function

Download Full-text

miR-30a inhibits the biological function of breast cancer cells by targeting Notch1

International Journal of Molecular Medicine ◽

10.3892/ijmm.2017.3084 ◽

2017 ◽

Vol 40 (4) ◽

pp. 1235-1242 ◽

Cited By ~ 6

Author(s):

He-Da Zhang ◽

Lin-Hong Jiang ◽

Da-Wei Sun ◽

Jian Li ◽

Jin-Hai Tang

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Biological Function

Download Full-text

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

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02898-4 ◽

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.

Download Full-text

MiR-139-5p inhibits the biological function of breast cancer cells by targeting Notch1 and mediates chemosensitivity to docetaxel

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2015.08.053 ◽

2015 ◽

Vol 465 (4) ◽

pp. 702-713 ◽

Cited By ~ 50

Author(s):

He-da Zhang ◽

Da-wei Sun ◽

Ling Mao ◽

Jun Zhang ◽

Lin-hong Jiang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Biological Function

Download Full-text

Nuclear distribution of eIF3g and its interacting nuclear proteins in breast cancer cells

Molecular Medicine Reports ◽

10.3892/mmr.2016.4935 ◽

2016 ◽

Vol 13 (4) ◽

pp. 2973-2980 ◽

Cited By ~ 7

Author(s):

QIAOLI ZHENG ◽

HAO LIU ◽

JINGJIA YE ◽

HUI ZHANG ◽

ZHENYU JIA ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Nuclear Proteins ◽

Nuclear Distribution

Download Full-text

Role of cytoplasmic localization of maspin in promoting cell invasion in breast cancer with aggressive phenotype

Scientific Reports ◽

10.1038/s41598-021-90887-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tomohiko Sakabe ◽

Makoto Wakahara ◽

Goshi Shiota ◽

Yoshihisa Umekita

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Invasion ◽

Breast Cancer Cells ◽

Biological Function ◽

Breast Cancer Cell Lines ◽

Cytoplasmic Localization ◽

Mesenchymal Transition ◽

Aggressive Phenotype

AbstractMammary serine protease inhibitor (maspin) is a tumor suppressor gene that is downregulated during carcinogenesis and breast cancer progression. While the nuclear localization of maspin is essential for tumor suppression, we previously reported that the cytoplasmic localization of maspin was significantly correlated with poor prognosis in breast cancer patients. To understand the mechanisms that underlie oncogenic role of cytoplasmic maspin, we studied its biological function in breast cancer cell lines. Subcellular localization of maspin in MDA-MB-231 breast cancer cells was mainly detected in the cytoplasm, whereas in MCF10A mammary epithelial cells, maspin was present in both cytoplasm and nucleus. In MDA-MB-231 cells, maspin overexpression promoted cell proliferation and cell invasion, whereas maspin downregulation resulted in the opposite effect. Further, we observed that SRGN protein levels were increased in MDA-MB-231 cells stably overexpressing maspin. Finally, maspin overexpression in MDA-MB-231 cells resulted in the N-cadherin and epithelial mesenchymal transition (EMT)-related transcription factors upregulation, and TGFβ signaling pathway activation. These results suggested that cytoplasmic maspin enhances the invasive and metastatic potential in breast cancer cells with aggressive phenotype by inducing EMT via SRGN/TGFβ axis. This study demonstrated a novel biological function of cytoplasmic maspin in progression of breast cancer cells with an aggressive phenotype.

Download Full-text