Runx1 is associated with breast cancer progression in MMTV-PyMT transgenic mice and its depletion in vitro inhibits migration and invasion

Gillian Browne; Hanna Taipaleenmäki; Nicole M. Bishop; Sharath C. Madasu; Leslie M. Shaw; Andre J. van Wijnen; Janet L. Stein; Gary S. Stein; Jane B. Lian

doi:10.1002/jcp.24989

miR-140-5p Attenuates Hypoxia-Induced Breast Cancer Progression by Targeting Nrf2/HO-1 Axis in a Keap1-Independent Mechanism

Cells ◽

10.3390/cells11010012 ◽

2021 ◽

Vol 11 (1) ◽

pp. 12

Author(s):

Megharani Mahajan ◽

Sandhya Sitasawad

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Cancer Progression ◽

Cellular Response ◽

Breast Cancer Progression ◽

Luciferase Assay ◽

Migration And Invasion ◽

Related Factor ◽

Hypoxic Conditions

Hypoxia and oxidative stress significantly contribute to breast cancer (BC) progression. Although hypoxia-inducible factor 1α (Hif-1α) is considered a key effector of the cellular response to hypoxia, nuclear factor erythroid 2–related factor 2 (Nrf2), a master antioxidant transcription factor, is a crucial factor essential for Hif-1α-mediated hypoxic responses. Hence, targeting Nrf2 could provide new treatment strategies for cancer therapy. miRNAs are potential regulators of hypoxia-responsive genes. In a quest to identify novel hypoxia-regulated miRNAs involved in the regulation of Nrf2, we found that miR-140-5p significantly affects the expression of Nrf2 under hypoxia. In our study, miR-140-5p expression is downregulated in BC cells under hypoxic conditions. We have identified Nrf2 as a direct target of miR-140-5p, as confirmed by the luciferase assay. Knockdown of miR-140-5p under normoxic conditions significantly enhanced Nrf2/HO-1 signaling and tumor growth, angiogenesis, migration, and invasion in BC. In contrast, overexpression of miR-140-5p under hypoxic conditions revealed opposite results. Further silencing Nrf2 expression mimicked the miR-140-5p-induced anti-tumor effects. Consistent with the knockdown of miR-140-5p in vitro, mice injected with miR-140-5p-KD cells exhibited dramatically reduced miR-140-5p levels, increased Nrf2 levels, and increased tumor growth. In contrast, tumor growth is potently suppressed in mice injected with miR-140-5p-OE cells. Collectively, the above results demonstrate the importance of the Nrf2/HO-1 axis in cancer progression and, thus, targeting Nrf2 by miR-140-5p could be a better strategy for the treatment of Nrf2-driven breast cancer progression.

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MaTAR25 LncRNA Regulates the Tensin1 Gene to Impact Breast Cancer Progression

10.1101/2020.02.03.931881 ◽

2020 ◽

Cited By ~ 1

Author(s):

Kung-Chi Chang ◽

Sarah D. Diermeier ◽

Allen T. Yu ◽

Lily D. Brine ◽

Suzanne Russo ◽

...

Keyword(s):

Breast Cancer ◽

Actin Cytoskeleton ◽

Cancer Progression ◽

Cancer Metastasis ◽

Focal Adhesions ◽

Breast Cancer Progression ◽

Migration And Invasion ◽

Mammary Tumor Cell ◽

Human Ortholog

SUMMARYMisregulation of long non-coding RNA genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin 1 (Tns1) to regulate its expression in trans. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. The human ortholog of MaTAR25, LINC01271, is upregulated with human breast cancer stage and metastasis.SIGNIFICANCELncRNAs have great potential to reveal new regulatory mechanisms of function as well as having exciting therapeutic capacity given their ease of being targeted by nucleic acid drugs. Our study of MaTAR25, and its human ortholog LINC01271, reveal an unexpected function of this lncRNA in breast cancer progression by regulating Tns1 gene expression, whose protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. We identified LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and cancer metastasis. Our findings demonstrate that LINC01271 represents an exciting therapeutic target to alter breast cancer progression.

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MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression

Nature Communications ◽

10.1038/s41467-020-20207-y ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Kung-Chi Chang ◽

Sarah D. Diermeier ◽

Allen T. Yu ◽

Lily D. Brine ◽

Suzanne Russo ◽

...

Keyword(s):

Breast Cancer ◽

Actin Cytoskeleton ◽

Cancer Progression ◽

Mammary Tumor ◽

Focal Adhesions ◽

Breast Cancer Progression ◽

Migration And Invasion ◽

Mammary Tumor Cell

AbstractMisregulation of long non-coding RNA (lncRNA) genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin1 (Tns1) to regulate its expression in trans. The Tns1 protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. We identify LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and metastasis. Our findings demonstrate that LINC01271 represents a potential therapeutic target to alter breast cancer progression.

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Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

Cancer Cell International ◽

10.1186/s12935-020-01733-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chen Hang ◽

Shanojie Zhao ◽

Tiejun Wang ◽

Yan Zhang

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Nuclear Accumulation ◽

Migration And Invasion ◽

Ubiquitin Protein Ligase ◽

Novel Target ◽

First Time ◽

Breast Tissues

Abstract Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

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LINC00665 promotes breast cancer progression through regulation of the miR-379-5p/LIN28B axis

Cell Death and Disease ◽

10.1038/s41419-019-2213-x ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 7

Author(s):

Wei Ji ◽

Yu-Ling Diao ◽

Yi-Ran Qiu ◽

Jie Ge ◽

Xu-Chen Cao ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Normal Breast ◽

Breast Cancer Progression ◽

Migration And Invasion ◽

Breast Tumorigenesis ◽

Mesenchymal Transition ◽

Tumorigenesis And Progression ◽

Mirna Sponges

AbstractBreast cancer is the most common malignant tumor among women worldwide. Although increasing evidence indicates that long noncoding RNAs (lncRNAs) play critical roles during breast tumorigenesis and progression, the involvement of most lncRNAs in breast cancer remains largely unknown. In the current study, we demonstrated that LINC00665 promotes breast cancer cell proliferation, migration, and invasion. Accumulating evidence indicates that many lncRNAs can function as endogenous miRNA sponges by competitively binding common miRNAs. In this study, we demonstrated that LINC00665 functions as a sponge for miR-379-5p, reducing the ability of miR-379-5p to repress LIN28B. LINC00665 promoted breast cancer progression and induced an epithelial–mesenchymal transition-like phenotype via the upregulation of LIN28B expression. Clinically, LINC00665 expression was increased but miR-379-5p expression was decreased in breast cancer tissues compared with that in normal breast tissues in the TCGA database. Furthermore, the expression of LINC00665 was negatively related with miR-379-5p expression. Collectively, our results reveal the LINC00665–miR-379-5p–LIN28B axis and shed light on breast cancer therapy.

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The Inhibitory Effect of (−)-Epigallocatechin-3-Gallate on Breast Cancer Progression via Reducing SCUBE2 Methylation and DNMT Activity

Molecules ◽

10.3390/molecules24162899 ◽

2019 ◽

Vol 24 (16) ◽

pp. 2899 ◽

Cited By ~ 9

Author(s):

Jie Sheng ◽

Weilin Shi ◽

Hui Guo ◽

Wenlin Long ◽

Yuxin Wang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Inhibitory Effect ◽

Breast Cancer Progression ◽

Migration And Invasion ◽

Dependent Manner ◽

Complement Protein ◽

Epidermal Growth Factor Domain ◽

Potential Implication ◽

Egcg Treatment

Epigenetic modifications are important mechanisms responsible for cancer progression. Accumulating data suggest that (−)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, may hamper carcinogenesis by targeting epigenetic alterations. We found that signal peptide-CUB (complement protein C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor) domain-containing protein 2 (SCUBE2), a tumor suppressor gene, was hypermethylated in breast tumors. However, it is unknown whether EGCG regulates SCUBE2 methylation, and the mechanisms remain undefined. This study was designed to investigate the effect of EGCG on SCUBE2 methylation in breast cancer cells. We reveal that EGCG possesses a significantly inhibitory effect on cell viability in a dose- and time-dependent manner and presents more effects than other catechins. EGCG treatment resulted in enhancement of the SCUBE2 gene, along with elevated E-cadherin and decreased vimentin expression, leading to significant suppression of cell migration and invasion. The inhibitory effect of EGCG on SCUBE2 knock-down cells was remarkably alleviated. Further study demonstrated that EGCG significantly decreased the SCUBE2 methylation status by reducing DNA methyltransferase (DNMT) expression and activity. In summary, this study reported for the first time that SCUBE2 methylation can be reversed by EGCG treatment, finally resulting in the inhibition of breast cancer progression. These results suggest the epigenetic role of EGCG and its potential implication in breast cancer therapy.

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Salinomycin inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vitro and in vivo

Biochemical Pharmacology ◽

10.1016/j.bcp.2019.04.026 ◽

2019 ◽

Vol 164 ◽

pp. 326-335 ◽

Cited By ~ 7

Author(s):

Jayant Dewangan ◽

Sonal Srivastava ◽

Sakshi Mishra ◽

Aman Divakar ◽

Sadan Kumar ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Tumor Angiogenesis ◽

Breast Cancer Progression

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Erythropoietin and Breast Cancer Progression: An in vitro Study

Microscopy and Microanalysis ◽

10.1017/s1431927611002388 ◽

2011 ◽

Vol 17 (S2) ◽

pp. 302-303

Author(s):

J Obayemi ◽

A Calabro ◽

C Queenan ◽

D Becker ◽

D Leonardi

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

In Vitro Study ◽

Breast Cancer Progression ◽

Vitro Study

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011.

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Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression

BioMed Research International ◽

10.1155/2015/161508 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 28

Author(s):

Sabrina Bimonte ◽

Antonio Barbieri ◽

Domenica Rea ◽

Giuseppe Palma ◽

Antonio Luciano ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Mouse Model ◽

Cancer Progression ◽

Breast Cancer Progression ◽

Cancer Cell Growth ◽

Patients With Cancer ◽

Human Breast Carcinoma Cells

Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Severalin vitroandin vivostudies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performedin vitrostudies on ER-negative human breast carcinoma cells, MDA.MB231 andin vivostudies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphinein vitroenhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells.In vivostudies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression.

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