Dynamics of Akt isoforms and role of Immune Evader (RCAS 1) in different grades of Breast Cancer tissues in Pakistani Women

Abstract Background and AimsPseudopodium-enriched atypical kinase 1 (PEAK1) has reported to be upregulated in human malignancies and related with poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is not clear. Here, we investigated the PEAK1 expression in breast cancer and analyzed its relation with clinicopathological status and chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated the role of PEAK1 on breast cancer cells in vitro and in vivo. MethodsImmunohistochemistry (IHC) was performed in 112 surgical resected breast cancer tissues. The associations between clinicopathological status, multi-drug resistance and PEAK1 expression were determined. Effect of PEAK1 overexpression or down-expression on proliferation, colony formation, invasion, migration, metastasis and Doxorubicin sensitivity in the MCF-7 cells in vitro and in vivo was detected. ResultsPEAK1 was overexpressed in breast cancer tissues and NAC -resistant breast cancer tissues. High PEAK1 expression was related with tumor size, high tumor grade, T stage, LN metastasis, recurrence, Ki-67 expression, Her-2 expression and multi-drug resistance. Targeting PEAK1 inhibited cell growth, invasion, metastasis and reversed chemoresistance to Doxorubicin in breast cancer cells in vitro and in vivo. ConclusionHigh PEAK1 expression was associated with invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 could inhibit cell growth and metastasis, and reverse chemoresistance in breast cancer cells, which provides an effective treatment strategies for breast cancer.

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MiR-133 Targets YES1 and Inhibits the Growth of Triple-Negative Breast Cancer Cells

Technology in Cancer Research & Treatment ◽

10.1177/1533033820927011 ◽

2020 ◽

Vol 19 ◽

pp. 153303382092701

Author(s):

Guochen Zhang ◽

Junlan Wang ◽

Ruilin Zheng ◽

Beibei Song ◽

Li Huang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Colony Formation ◽

Breast Cancer Cells ◽

Triple Negative ◽

Mechanism Study ◽

Inhibitory Effects ◽

Cancer Tissues

Triple-negative breast cancer shows worse outcome compared with other subtypes of breast cancer. The discovery of dysregulated microRNAs and their roles in the progression of triple-negative breast cancer provide novel strategies for the treatment of patients with triple-negative breast cancer. In this study, we identified the significant reduction of miR-133 in triple-negative breast cancer tissues and cell lines. Ectopic overexpression of miR-133 suppressed the proliferation, colony formation, and upregulated the apoptosis of triple-negative breast cancer cells. Mechanism study revealed that the YES Proto-Oncogene 1 was a target of miR-133. miR-133 bound the 3′-untranslated region of YES Proto-Oncogene 1 and decreased the level of YES Proto-Oncogene 1 in triple-negative breast cancer cells. Consistent with miR-133 downregulation, YES1 was significantly increased in triple-negative breast cancer, which was inversely correlated with the level of miR-133. Restoration of YES Proto-Oncogene 1 attenuated the inhibitory effects of miR-133 on the proliferation and colony formation of triple-negative breast cancer cells. Consistent with the decreased expression of YES Proto-Oncogene 1, overexpression of miR-133 suppressed the phosphorylation of YAP1 in triple-negative breast cancer cells. Our results provided novel evidence for the role of miR-133/YES1 axis in the development of triple-negative breast cancer, which indicated miR-133 might be a potential therapeutic strategy for triple-negative breast cancer.

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Circular RNA circVAPA regulates breast cancer cell migration and invasion via sponging miR-130a-5p

Epigenomics ◽

10.2217/epi-2019-0124 ◽

2020 ◽

Vol 12 (4) ◽

pp. 303-317 ◽

Cited By ~ 8

Author(s):

Si-ying Zhou ◽

Wei Chen ◽

Su-jin Yang ◽

Jian Li ◽

Jun-ying Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Circular Rna ◽

Migration And Invasion ◽

Mirna Sponge ◽

Cell Migration And Invasion ◽

Cancer Migration ◽

Cancer Tissues ◽

The Relationship

Aim: We aimed to explore the roles of circular RNA, circVAPA in regulating cell migration and invasion of breast cancer. Materials & methods: CircVAPA expression was detected in breast cancer tissues and cells. The role of circVAPA was evaluated by MTT assay, wound-healing and transwell assay. The relationship between circVAPA and miR-130a-5p and the location of circVAPA were explored. Results: We discovered that circVAPA was dysregulated in breast cancer tissues and cells. Ectopic circVAPA regulated breast cancer migration, invasion and proliferation. CircVAPA was mainly expressed in the cytoplasm and could act as a miRNA sponge for miR-130a-5p, but did not regulate its parental gene. Conclusion: CircVAPA may promote migration and invasion capacity of breast cancer via harboring miR-130a-5p.

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Expression of MALAT1 Promotes Trastuzumab Resistance in HER2 Overexpressing Breast Cancers

Cancers ◽

10.3390/cancers12071918 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1918

Author(s):

Yanyuan Wu ◽

Marianna Sarkissyan ◽

Ochanya Ogah ◽

Juri Kim ◽

Jaydutt V. Vadgama

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Akt Pathway ◽

Breast Cancers ◽

Trastuzumab Resistance ◽

Mesenchymal Transition ◽

Cancer Tissues

Background: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is associated with cancer progression. Our study examined the role of MALAT1 in breast cancer and the mechanisms involved in the regulation of MALAT1. Methods: In vitro cell and in vivo animal models were used to examine the role of MALAT1 in breast cancer. The interaction of FOXO1 (Forkhead Box O1) at the promoter region of MALAT1 was investigated by chromatin immunoprecipitation (ChIP) assay. Results: The data shows an elevated expression of MALAT1 in breast cancer tissues and cells compared to non-cancer tissues and cells. The highest level of MALAT1 was observed in metastatic triple-negative breast cancer and trastuzumab-resistant HER2 (human epidermal growth factor receptor 2) overexpressing (HER2+) cells. Knockdown of MALAT1 in trastuzumab-resistant HER2+ cells reversed epithelial to mesenchymal transition-like phenotype and cell invasiveness. It improved the sensitivity of the cell’s response to trastuzumab. Furthermore, activation of Akt by phosphorylation was associated with the upregulation of MALAT1. The transcription factor FOXO1 regulates the expression of MALAT1 via the PI3/Akt pathway. Conclusions: We show that MALAT1 contributes to HER2+ cell resistance to trastuzumab. Targeting the PI3/Akt pathway and stabilizing FOXO1 translocation could inhibit the upregulation of MALAT1.

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Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence

Oncotarget ◽

10.18632/oncotarget.1936 ◽

2014 ◽

Vol 5 (20) ◽

pp. 9678-9688 ◽

Cited By ~ 24

Author(s):

Mauro Finicelli ◽

Giovanni Benedetti ◽

Tiziana Squillaro ◽

Barbara Pistilli ◽

Andrea Marcellusi ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Marker ◽

Primary Breast Cancer ◽

Early Recurrence ◽

Cancer Tissues

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Transition into inflammatory cancer-associated adipocytes in breast cancer microenvironment requires microRNA regulatory mechanism

10.1101/089243 ◽

2016 ◽

Author(s):

Jiwoo Lee ◽

Han Suk Ryu ◽

Bok Sil Hong ◽

Han-Byoel Lee ◽

Minju Lee ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Regulatory Mechanism ◽

Luciferase Reporter ◽

Cancer Microenvironment ◽

Human Breast ◽

Cancer Tissues

ABSTRACTSIntroductionThe role of adipocytes in cancer microenvironment has gained focus during the recent years. However, the characteristics of the cancer-associated adipocytes (CAA) in human breast cancer tissues and the underlying regulatory mechanism are not clearly understood.MethodWe reviewed pathology specimens of breast cancer patients to understand the morphologic characteristics of CAA, and profiled the mRNA and miRNA expression of CAA by using indirect co-culture system in vitro.ResultsThe CAAs in human breast cancers showed heterogeneous topographic relationship with breast cancer cells within the breast microenvironment. The CAAs exhibited the characteristics of de-differentiation determined by their microscopic appearance and the expression levels of adipogenic markers. Additionally, the 3T3-L1 adipocytes co-cultured with breast cancer cells showed up-regulation of inflammation-related genes including Il6 and Ptx3. The up-regulation of IL6 in CAA was further observed in human breast cancer tissues. miRNA array of co-cultured 3T3-L1 cells showed increased expression of mmu-miR-5112 which may target Cpeb1. Cpeb1 is a negative regulator of Il6. The suppressive role of mmu-miR-5112 was confirmed by dual luciferase reporter assay, and mmu-miR-5112-treated adipocytes showed up-regulation of Il6. The transition of adipocytes into more inflammatory CAA resulted in proliferation-promoting effect in ER positive breast cancer cells such as MCF7 and ZR-75-1 but not in ER negative cells.ConclusionIn this study, we have determined the de-differentiated and inflammatory natures of CAA in breast cancer microenvironment. Additionally, we propose a miRNA-based regulatory mechanism underlying the process of acquiring inflammatory phenotypes in CAA.

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Knock Down of LINC00504 Represses Proliferation and Invasion via Regulation of miR-140-5p in Breast Cancer

10.21203/rs.3.rs-39231/v1 ◽

2020 ◽

Author(s):

Tieying Hou ◽

Long Ye ◽

Qingsong Qin ◽

Shulin Wu

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Breast Cancer Cell ◽

Migration And Invasion ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Cancer Tissues ◽

Proliferation And Invasion

Abstract Background: Breast cancer is one of the most common cancer in the world. Emerging evidence has demonstrated the critical role of long noncoding RNAs (lncRNAs) in the development of breast cancer. In this study, we aimed to investigate the role of LINC00504 in breast cancer progression. Methods: Quantification real-time PCR was used to analyzed the expression levels of LINC00504 and miR‐140-5p in breast cancer tissues and cell lines. Cell proliferation, migration and invasion were assessed by Cell Counting Kit‐8, transwell assay and Immunofluorescence. Dual-luciferase reporter assay and RNA Immunoprecipitation assay were performed to verify the interaction between LINC00504 and miR‐140-5p. The expression levels of VEGFA, CDH1 and VIM were demonstrated by western blot assays. Result: Here, we found that LINC00504 is up regulated in breast cancer tissues and cell lines. Down regulation of LINC00504 mediated by shRNA suppressed the proliferation, migration, and invasion of breast cancer cells in vitro and in vivo. Furthermore, LINC00504 was found to competitively regulate miR‐140-5p via targeting VEGFA. Inhibition of miR‐140-5p attenuated the knockdown-LINC00504 induced inhibition of breast cancer cell proliferation and invasion.Conclusion: Taken together, our results demonstrated the mechanism of the LINC00504–miR‐140-5p–VEGFA axis in breast cancer cell proliferation and invasion and may lead to new lncRNA-based diagnostics or therapeutics for breast cancer.

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Evaluating the expression level of HERV-K env, np9, rec and gag in breast tissue

Infectious Agents and Cancer ◽

10.1186/s13027-019-0260-7 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 3

Author(s):

Shaian Tavakolian ◽

Hossein Goudarzi ◽

Ebrahim Faghihloo

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Breast Tissue ◽

Mrna Level ◽

Critical Role ◽

Expression Level ◽

Significant Elevation ◽

Diagnose Breast Cancer ◽

Cancer Tissues

Abstract Objective Breast cancer is one of the most common health problems. It has been suggested that several risk factors, either considered as external or internal, play a critical role in the pathogenesis of breast cancer, which among them, HERV-k, has the most fundamental role. In the present study, we aimed to evaluate the role of HERV-k env, gag, rec, np9 expressions in breast cancer progression. Materials and methods We collected 40 breast cancer tissues and their normal adjacent ones. After extracting the RNA of breast samples, we evaluated the expression of HERV-k env, gag, rec, np9 by using Quantitative real-time PCR (qRT-PCR). Results The resulting data revealed that while there was a meaningful increase in the expression level of HERV-k env, gag and np9 in breast cancer tissues (P ≤ 0.01, 0.05, 0.05, respectively), we failed to find any significant elevation in the expression level of rec mRNA level. Conclusion The results of our study suggested that there is a plausible correlation between the mRNA expression level of HERV-K env, gag and np9 and the progression of breast cancer, proposing these markers as promising biomarkers to diagnose breast cancer.

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Dual Aromatase-Sulphatase Inhibitors (DASIs) for the Treatment of Hormone Dependent Breast Cancer

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666210119123840 ◽

2021 ◽

Vol 21 ◽

Author(s):

Laxmi Banjare ◽

Akhlesh Kumar Jain ◽

Suresh Thareja

Keyword(s):

Breast Cancer ◽

Dehydroepiandrosterone Sulfate ◽

Develop Breast Cancer ◽

Estrone Sulfate ◽

Cancer Tissues ◽

Breast Cancer Inhibition ◽

Estrogen Biosynthesis ◽

Breast Tissues ◽

Cancer Inhibition

: Breast cancer is the most frequent diagnosed cancer in women and the second most common form of cancer, causing death after lung cancer, all across the globe at an alarming rate. The level of estrogens, in breast cancer tissues of postmenopausal women is 10-40 folds higher than the non-carcinogenic breast tissues. As a result of this greater level of estrogen, breast tissue becomes more prone to develop breast cancer; mainly estradiol plays a significant role in the initiation and development of hormone dependent breast cancer. Androstenedione, Adrenal dehydroepiandrosterone sulfate and estrone-sulfate also plays an important role of precursor for estrogen biosynthesis. Estrogens deprivation exhibits an attractive phenomena in the advancement of most ideal therapeutics for the treatment of breast cancer. Inhibition of aromatase and sulphatase emerged as attractive therapy for the treatment of hormone dependent breast cancer via deprivation of estrogen by different pathways. The cocktail of aromatase and sulphatase inhibitors known as dual aromatase-sulphatase inhibitors (DASIs) emerged as an attractive approach for the effective estrogen deprivation. The present review article focused on the journey of dual aromatase-sulphatase inhibitors from the beginning to till date (2020). Keeping in view the key observations, this review may be helpful for medicinal chemists to design and develop new and efficient dual aromatase-sulphatase inhibitors for the possible treatment of hormone-related breast cancer.

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Increased Extracellular Adenosine in Radiotherapy-Resistant Breast Cancer Cells Enhances Tumor Progression through A2AR-Akt-b-Catenin Signaling

Cancers ◽

10.3390/cancers13092105 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2105

Author(s):

Hana Jin ◽

Jong Sil Lee ◽

Dong Chul Kim ◽

Young Shin Ko ◽

Gyeong Won Lee ◽

...

Keyword(s):

Breast Cancer ◽

Adenosine Diphosphate ◽

Dependent Manner ◽

Vimentin Expression ◽

Extracellular Adenosine ◽

Akt Phosphorylation ◽

4T1 Cells ◽

Cancer Tissues

Recently, we found that the expressions of adenosine (ADO) receptors A2AR and A2BR and the ectonucleotidase CD73 which is needed for the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and the extracellular ADO level are increased in TNBC MDA-MB-231 cells and RT-R-MDA-MB-231 cells compared to normal cells or non-TNBC cells. The expression of A2AR, but not A2BR, is significantly upregulated in breast cancer tissues, especially TNBC tissues, compared to normal epithelial tissues. Therefore, we further investigated the role of ADO-activated A2AR and its signaling pathway in the progression of RT-R-TNBC. ADO treatment induced MDA-MB-231 cell proliferation, colony formation, and invasion, which were enhanced in RT-R-MDA-MB-231 cells in an A2AR-dependent manner. A2AR activation by ADO induced AKT phosphorylation and then b-catenin, Snail, and vimentin expression, and these effects were abolished by A2AR-siRNA transfection. In an in vivo animal study, compared to 4T1-injected mice, RT-R-4T1-injected mice exhibited significantly increased tumor growth and lung metastasis, which were decreased by A2AR-knockdown. The upregulation of phospho-AKT, b-catenin, Snail, and vimentin expression in mice injected with RT-R-4T1 cells was also attenuated in mice injected with RT-R-4T1-A2AR-shRNA cells. These results suggest that A2AR is significantly upregulated in BC tissues, especially TNBC tissues, and ADO-mediated A2AR activation is involved in RT-R-TNBC invasion and metastasis through the AKT-β-catenin pathway.

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