miR-375 inhibits cancer stem cell phenotype and tamoxifen resistance by degrading HOXB3 in human ER-positive breast cancer

Fu, Hui; Fu, Lei; Xie, Chao; Zuo, Wenqi; Liu, Yansong; Zheng, Min; Yu, Jinming

doi:10.3892/or.2017.5360

Cited by 60 publications

(46 citation statements)

References 34 publications

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“…Notably, while tamoxifen repressed miR-27b expression, estrogen induced miR-27b in BC cells (422). We already illustrated above miR-375, that can modulate the sensitivity/resistance of drug treatments in different cancers, including BC (193) and MTC (196). At the same time an anticancer treatment like alitretinoin may exert a regulatory action on miR-375 expression in BC cells (195).…”

Section: Drugs/non-coding Rnas Subnetworkmentioning

confidence: 99%

“…Furthermore, miR-375 partly reversed the EMT process: metadherin (MTDH) was identified as a direct target of miR-375 and tamoxifen-treated patients with higher MTDH had a higher risk of relapse (192). Another miR-375 target is HOXB3; miR-375 inhibited cancer stem cells (CSCs) phenotype and tamoxifen resistance by regulating CSCs, through degradation of HOXB3 (193). Epigenetically down-regulated miR-375 in HER2-positive BC could induce trastuzumab resistance by targeting IGF1R (194).…”

Section: A Network Analysis: the Most Central Ncrnas In Chemoresistancementioning

confidence: 99%

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The Network of Non-coding RNAs in Cancer Drug Resistance

et al. 2018

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Non-coding RNAs (ncRNAs) have been implicated in most cellular functions. The disruption of their function through somatic mutations, genomic imprinting, transcriptional and post-transcriptional regulation, plays an ever-increasing role in cancer development. ncRNAs, including notorious microRNAs, have been thus proposed to function as tumor suppressors or oncogenes, often in a context-dependent fashion. In parallel, ncRNAs with altered expression in cancer have been reported to exert a key role in determining drug sensitivity or restoring drug responsiveness in resistant cells. Acquisition of resistance to anti-cancer drugs is a major hindrance to effective chemotherapy and is one of the most important causes of relapse and mortality in cancer patients. For these reasons, non-coding RNAs have become recent focuses as prognostic agents and modifiers of chemo-sensitivity. This review starts with a brief outline of the role of most studied non-coding RNAs in cancer and then highlights the modulation of cancer drug resistance via known ncRNAs based mechanisms. We identified from literature 388 ncRNA-drugs interactions and analyzed them using an unsupervised approach. Essentially, we performed a network analysis of the non-coding RNAs with direct relations with cancer drugs. Within such a machine-learning framework we detected the most representative ncRNAs-drug associations and groups. We finally discussed the higher integration of the drug-ncRNA clusters with the goal of disentangling effectors from downstream effects and further clarify the involvement of ncRNAs in the cellular mechanisms underlying resistance to cancer treatments.

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Section: Drugs/non-coding Rnas Subnetworkmentioning

confidence: 99%

Section: A Network Analysis: the Most Central Ncrnas In Chemoresistancementioning

confidence: 99%

The Network of Non-coding RNAs in Cancer Drug Resistance

et al. 2018

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“…For instance, miR‐221/222 has been shown to target ERα and contributes to tamoxifen resistance . Restoration of miR‐375 reverses tamoxifen resistance in breast cancer by MTDH . The identification of estrogen‐regulated and tamoxifen resistance‐associated miRNAs is beneficial for understanding the underlying molecular mechanisms associated with ER+ breast cancer development and progression.…”

Section: Introductionmentioning

confidence: 99%

miR‐191/DAB2 axis regulates the tumorigenicity of estrogen receptor‐positive breast cancer

Tian

Zhang

2017

IUBMB Life

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Disabled-2 (DAB2) has been shown to be downregulated in a variety of human cancer types including breast tumors. However, the role of DAB2 in estrogen receptor positive (ER+) breast cancer cells has not been reported. In this context, we demonstrated that DAB2 expression was significantly decreased in ER+ breast cancer cell lines and ER+ clinical specimens, compared with ER- breast cancer cell lines and ER- tissues, respectively. Depletion of estrogen significantly elevated DAB2 expression in ER+ MCF7 and T-47D cells. Treatment with estradiol (E2) reduced the expression of DAB2 and administration of tamoxifen upregulated DAB2 expression in a dose-dependent manner. Functionally, silencing of DAB2 in hormone-starved MCF7 and T-47D cells promoted cellular proliferation and enforced expression of DAB2 in normal-cultured or E2-treated cells suppressed cellular proliferation. Mechanistically, estrogen-induced miR-191 was identified as a direct upstream regulator of DAB2 in ER+ cells. Luciferase reporter assay indicated that miR-191 inhibited DAB2 expression by directly targeting the 3'-UTR of DAB2. Importantly, the expression and function of miR-191 showed the opposite tendency with DAB2 in ER+ cells. In vivo, inhibition of miR-191 significantly suppressed the xenograft growth induced by E2, and silencing of DAB2 could restored the growth arrest induced by miR-191 inhibition. Taken together, our data unveil that the miR-191-DAB2 axis seems to be an important pathway associated with estrogen signaling in breast cancer and may serve as a potential diagnostic biomarker and a powerful therapeutic target for ER+ breast cancer patients. © 2017 IUBMB Life, 70(1):71-80, 2018.

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“…HOXB3 has different effects in promoting cancer or suppressing cancer in different types of tumors. Hui Fu [19] and others found that HOXB3 is a target of miR-375 in MCF-7 cells. Moreover, HOXB3 could not only signi cantly promote EMT in MCF-7 cells, but also promote the formation of CSC phenotype and tamoxifen resistance.…”

Section: Discussionmentioning

confidence: 97%

Loss of HOXB3 promotes development of hormone receptor negative breast cancer

Zhu¹,

Yu²,

Jiang³

et al. 2020

Preprint

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BackgroundThe homobox (HOX) gene family as a transcription factor encoding a specific nuclear protein is essential for embryonic development, differentiation, and homeostasis. The role of HOXB3 protein varies in different tumors. This study aims to explore the role of the HOXB3 gene in breast cancer.MethodDifferentiated expressed genes were screened by analyzing metastatic breast cancer gene chip data in TCGA and GEO database. The function of selected HOXB3 gene was also analyzed by GEPIA, Kaplan-Meier Plotter, Breast Cancer Gene-Expression Miner and metascape. Molecular biology methods such as qRT-PCR, western blot and IF was used to verify bio-informatics findings.ResultsBoth bio-informatics analyses and western blot showed that HOXB3 was lost in breast cancer compared to normal breast tissue. Survival analysis also showed that lower expression of HOXB3 was associated with poor prognosis. Bio-informatics analyses further showed that HOXB3 was positively correlated with hormone receptors. qRT-PCR, immunofluorescence and western blot also confirmed that HOXB3 had the highest expression in the immortalized breast epithelial cell line MCF-10A, lower in luminal breast cancer cell line T47D and the lowest in triple negative breast cancer (TNBC) cell line MDA-MB-231. Metascape for GO analysis of GEO data provided possible mechanism that HOXB3 could positively regulate cell adhesion, inhibit cell proliferation and activate immune response in breast cancer, and considered that HOXB3 might cause cell malignant transformation through the above pathways.ConclusionIn summary, HOXB3 expression was decreased in breast cancer, especially in hormone receptor-negative breast cancer. The lower expression of HOXB3 was associated with poor prognosis. It might become a new biomarker to predict prognosis of breast cancer.

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miR-375 inhibits cancer stem cell phenotype and tamoxifen resistance by degrading HOXB3 in human ER-positive breast cancer

Cited by 60 publications

References 34 publications

The Network of Non-coding RNAs in Cancer Drug Resistance

The Network of Non-coding RNAs in Cancer Drug Resistance

miR‐191/DAB2 axis regulates the tumorigenicity of estrogen receptor‐positive breast cancer

Loss of HOXB3 promotes development of hormone receptor negative breast cancer

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