YB-1 interplays with ERα to regulate the stemness and differentiation of ER-positive breast cancer stem cells

Yang, Fan; Chen, Siqi; He, Shengnan; Huo, Qin; Hu, Ye; Xie, Ni

doi:10.7150/thno.41014

Cited by 28 publications

(32 citation statements)

References 46 publications

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“…Since inhibition of TIE2 was found to result in inhibition of cancer cell migration and tumour invasion in our previous findings, 39 , 40 the anti-metastatic effect of MSN-siRNA/Apt was assessed in vitro. Notably, Dox was found to impact cell migration and invasion in previous studies; 41 , 42 consequently, Dox was not loaded into the siRNA formulations in our in vitro anti-metastasis study.…”

Section: Resultsmentioning

confidence: 97%

Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

Liu¹,

Chen²,

Hu³

et al. 2021

IJN

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Introduction Metastatic breast cancer seriously harms women’s health and is currently the tumour type with the highest mortality rate in women. Recently, the combinatorial therapeutic approaches that integrate anti-cancer drugs and genetic agents is an attractive and promising strategy for the treatment of metastatic breast cancer. Moreover, such a combination strategy requires better drug carriers that can effectively deliver the cargo to the breast cancer cells and achieve controlled release in the cells to achieve better therapeutic effects. Methods The tumour-targeted and redox-responsive mesoporous silica nanoparticles (MSNs) functionalised with DNA aptamers (AS1411) as a co-delivery system was developed and investigated for the potential against metastatic breast cancer. Doxorubicin (Dox) was loaded onto the MSNs, while AS1411 and a small interfering RNA (siTIE2) were employed as gatekeepers via attachment to the MSNs with redox-sensitive disulfide bonds. Results The controlled release of Dox and siTIE2 was associated with intracellular glutathione. AS1411 mediated the targeted delivery of Dox by increasing its cellular uptake in metastatic breast cancer, ultimately resulting in a lower IC50 in MDA-MB-231 cells (human breast cancer cell line with high metastatic potency), improved biodistribution in tumour-bearing mice, and enhanced in vivo anti-tumour effects. The in vitro cell migration/invasion assay and in vivo anti-metastatic study revealed synergism in the co-delivery system that suppresses cancer cell metastasis. Conclusion The tumour-targeted and redox-responsive MSN prepared in this study are promising for the effective delivery and controlled release of Dox and siTIE2 for improved treatment of metastatic breast cancer.

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Section: Resultsmentioning

confidence: 97%

Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

Liu¹,

Chen²,

Hu³

et al. 2021

IJN

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“…Consistent with previous studies in other cancers 13 - 15 , we demonstrated that miR-575 promoted tumor growth and reduced tamoxifen resistance in ER+ breast cancer in in vitro and in vivo experiments, suggesting an oncogenic role for miR-575. Estrogen is essential in the hormone-dependent breast cancer development and progression, and more than approximately 70% of breast tumors express ER and are prone to exhibit resistance to anti-estrogen therapies 22 , 23 . Thus, the identification of estrogen/ERα and miRNA correlations may facilitate the development of predictive biomarkers and novel therapeutic targets 24 .…”

Section: Discussionmentioning

confidence: 99%

The ERα-miR-575-p27 feedback loop regulates tamoxifen sensitivity in ER-positive Breast Cancer

Liu

Zhang

et al. 2020

Theranostics

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Background: Breast cancer is the most common malignancy, and approximately 70% of breast cancers are estrogen receptor-α (ERα) positive. The anti-estrogen tamoxifen is a highly effective and commonly used treatment for patients with ER+ breast cancer. However, 30% of breast cancer patients fail adjuvant tamoxifen therapy and most of metastatic breast cancer patients develop tamoxifen resistance. Although increasing evidence suggests that microRNA (miRNA) dysregulation influences tamoxifen sensitivity, the mechanism of the cross-talk between miRNA and ERα signaling remains unclear. miR-575 has been reported to be involved in carcinogenesis and progression, however, the role of miR-575 in breast cancer remains limited. The aim of this study was to understand the mechanism of miR-575 in breast cancer tamoxifen resistance. Method: RT-qPCR was employed to assess miR-575 expression in breast cancer tissues and cell lines. The association of miR-575 expression with overall survival in patients with breast cancer was evaluated with KM plotter. Additionally, the effects of miR-575 on breast cancer proliferation and tamoxifen sensitivity were investigated both in vitro and in vivo . Bioinformatic analyses and luciferase reporter assays were performed to validate CDKN1B and BRCA1 as direct targets of miR-31-5p. The ERα binding sites in the miR-575 promoter region was validated with ChIP and luciferase assays. ERα interactions with CDKN1B, cyclin D1 or BRCA1 were determined by IP analysis, and protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Results: miR-575 levels were higher in ER+ breast cancer than in ER- breast cancer and patients with high miR-575 expression had a significantly poorer outcome than those with low miR-575 expression. ERα bound the miR-575 promoter to activate its transcription, and tamoxifen treatment downregulated miR-575 expression in ER+ breast cancer. Overexpression of miR-575 decreased tamoxifen sensitivity by targeting CDKN1B and BRCA1. CDKN1B and BRCA1 were both able to antagonize ERα activity by inhibiting ERα nuclear translocation and interaction with cyclin D1. Furthermore, miR-575 expression was found to be upregulated in ER+ breast cancer cell with acquired tamoxifen resistance, whereas depletion of miR-575 partially re-sensitized these cells to tamoxifen by regulation of CDKN1B. Conclusions: Our data reveal the ERα-miR-575-CDKN1B feedback loop in ER+ breast cancer, suggesting that miR-575 can be used as a prognostic biomarker in patients with ER+ breast cancer, as well as a predictor or a promising target for tamoxifen sensitivity.

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“…Accumulating studies have shown that SCUBE3 is closely related to the invasion and metastasis of lung cancer. It mainly triggers the TGF-β pathway, and then promotes tumor angiogenesis, epithelial-mesenchymal transition (EMT) [11,12] and angiogenesis [13]. More recently, the survival time of NSCLC patients with high expression of SCUBE3 was signi cantly shorter than that of NSCLC patients with low expression of SCUBE3, which supports the expression of SCUBE3 as an independent prognostic factor of NSCLC [14].…”

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confidence: 92%

SCUBE3 Serves as an Independent Poor Prognostic Factor in Breast Cancer

Huo

He²,

et al. 2020

Preprint

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Background: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by univariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. SCUBE3 expression was significantly correlated with ER (p = 0.018), PR (p = 0.015), HER2 (p = 0.039), and triple-negative status (p = 0.049) of patients with breast cancer. We further verified that the expression levels of SCUBE3 mRNA was significantly correlated with ER (p = 0.0007), PR (p = 0.0295), and triple-negative (p = 0.0024), respectively. There was no significant expression difference in the expression of SCUBE3 mRNA in age, HER2 receptor status, and nodal status (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2+ (p = 0.007). The univariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI: 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI: 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.Conclusions: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

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YB-1 interplays with ERα to regulate the stemness and differentiation of ER-positive breast cancer stem cells

Cited by 28 publications

References 46 publications

Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

The ERα-miR-575-p27 feedback loop regulates tamoxifen sensitivity in ER-positive Breast Cancer

SCUBE3 Serves as an Independent Poor Prognostic Factor in Breast Cancer

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YB-1 interplays with ERα to regulate the stemness and differentiation of ER-positive breast cancer stem cells

Cited by 28 publications

References 46 publications

Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

Tumour-Targeted and Redox-Responsive Mesoporous Silica Nanoparticles for Controlled Release of Doxorubicin and an siRNA Against Metastatic Breast Cancer

The ERα-miR-575-p27 feedback loop regulates tamoxifen sensitivity in ER-positive Breast Cancer

SCUBE3&nbsp;Serves as an Independent Poor Prognostic Factor in Breast Cancer

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SCUBE3 Serves as an Independent Poor Prognostic Factor in Breast Cancer