scholarly journals LncRNA RNA Component of Mitochondrial RNA-Processing Endoribonuclease Promotes AKT-Dependent Breast Cancer Growth and Migration by Trapping MicroRNA-206

2021 ◽  
Vol 9 ◽  
Author(s):  
Yingdan Huang ◽  
Bangxiang Xie ◽  
Mingming Cao ◽  
Hua Lu ◽  
Xiaohua Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Rna Processing ◽  
Cancer Development ◽  
Mitochondrial Rna ◽  
Cancer Cell Growth ◽  
Cell Growth And Migration ◽  
Downstream Target ◽  
And Migration ◽  
Proliferation And Migration

The RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) was recently shown to play a role in cancer development. However, the function and mechanism of RMRP during cancer progression remain incompletely understood. Here, we report that RMRP is amplified and highly expressed in various malignant cancers, and the high level of RMRP is significantly associated with their poor prognosis, including breast cancer. Consistent with this, ectopic RMRP promotes proliferation and migration of TP53-mutated breast cancer cells, whereas depletion of RMRP leads to inhibition of their proliferation and migration. RNA-seq analysis reveals AKT as a downstream target of RMRP. Interestingly, RMRP indirectly elevates AKT expression by preventing AKT mRNA from miR-206-mediated targeting via a competitive sequestering mechanism. Remarkably, RMRP endorses breast cancer progression in an AKT-dependent fashion, as knockdown of AKT completely abolishes RMRP-induced cancer cell growth and migration. Altogether, our results unveil a novel role of the RMRP-miR-206-AKT axis in breast cancer development, providing a potential new target for developing an anti-breast cancer therapy.

scholarly journals MIR22HG inhibits breast cancer progression by stabilizing LATS2 tumor suppressor

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Xiaochong Deng ◽  
Danrong Ye ◽  
Kaiyao Hua ◽  
Hongming Song ◽  
Qifeng Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Normal Breast ◽  
Breast Cancer Progression ◽  
Large Tumor ◽  
Downstream Target ◽  
And Migration ◽  
Proliferation And Migration

AbstractThe long noncoding RNA called MIR22 host gene (MIR22HG) was previously identified as a tumor suppressor in several cancers. However, the biological function of MIR22HG in breast cancer remains unknown. In this study, we aimed to determine the function and molecular mechanism of MIR22HG in breast cancer progression using transcriptomics and biotechnological techniques. Our results showed that MIR22HG expression was lower in the cancerous tissues than in the paired adjacent normal breast tissues. Additionally, MIR22HG was found to be mainly located in the cytoplasm and acted as a miR-629-5p sponge. Notably, MIR22HG stabilized the expression of large tumor suppressor 2 (LATS2), which promoted the LATS2-dependent phosphorylation of YAP1 and suppressed the expression of its downstream target oncogenes, thereby inhibiting the proliferation and migration of breast cancer cells. Therefore, our findings reveal the MIR22HG-dependent inhibition of breast cancer cell proliferation and migration via the miR-629-5p/LATS2 pathway, providing new insights and identifying novel therapeutic targets for breast cancer treatment.

scholarly journals p66α Suppresses Breast Cancer Cell Growth and Migration by Acting as Co-Activator of p53

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3593
Author(s):  
Qun Zhang ◽  
Yihong Zhang ◽  
Jie Zhang ◽  
Dan Zhang ◽  
Mengying Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Tumor Suppressor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Target Genes ◽  
Cancer Cell Growth ◽  
Cell Growth And Migration ◽  
Breast Cancer Cell Growth ◽  
And Migration

p66α is a GATA zinc finger domain-containing transcription factor that has been shown to be essential for gene silencing by participating in the NuRD complex. Several studies have suggested that p66α is a risk gene for a wide spectrum of diseases such as diabetes, schizophrenia, and breast cancer; however, its biological role has not been defined. Here, we report that p66α functions as a tumor suppressor to inhibit breast cancer cell growth and migration, evidenced by the fact that the depletion of p66α results in accelerated tumor growth and migration of breast cancer cells. Mechanistically, immunoprecipitation assays identify p66α as a p53-interacting protein that binds the DNA-binding domain of p53 molecule predominantly via its CR2 domain. Depletion of p66α in multiple breast cells results in decreased expression of p53 target genes, while over-expression of p66α results in increased expression of these target genes. Moreover, p66α promotes the transactivity of p53 by enhancing p53 binding at target promoters. Together, these findings demonstrate that p66α is a tumor suppressor by functioning as a co-activator of p53.

scholarly journals Aspirin Modifies Inflammatory Mediators and Metabolomic Profiles and Contributes to the Suppression of Obesity-Associated Breast Cancer Cell Growth

2020 ◽  
Vol 21 (13) ◽  
pp. 4652 ◽  
Author(s):  
Chia-Chien Hsieh ◽  
Huai-Hsuan Chiu ◽  
Chih-Hsuan Wang ◽  
Ching-Hua Kuo
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Fatty Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Growth ◽  
Cell Growth And Migration ◽  
Breast Cancer Cell Growth ◽  
And Migration

Breast cancer is the most common cancer among women. Adiposity generally accompanies immune cell infiltration and cytokine secretion, which is ideal for tumor development. Aspirin is a chemopreventive agent against several types of cancer. The aim of this study was to investigate whether aspirin inhibits the growth of 4T1 breast cancer cells by inhibiting the inflammatory response and regulating the metabolomic profile of 3T3-L1 adipocytes. 3T3-L1 adipocyte-conditioned medium (Ad-CM) was used to mimic the obese adipose tissue microenvironment in 4T1 cells. The results revealed that aspirin inhibited macrophage chemoattractant protein (MCP-1), interleukin (IL-6), IL-1β, and plasminogen activator inhibitor (PAI-1) production in 3T3-L1 adipocytes stimulated by tumor necrosis factor-alpha (TNF-α) and lipopolysaccharide (LPS). In the obesity-associated model, Ad-CM significantly promoted 4T1 cell growth and migration, which were attenuated after aspirin treatment. The results of metabolic analyses using Ad-CM showed that amino acid metabolites and oxidative stress were increased in mature 3T3-L1 adipocytes compared to those in fibroblasts. Aspirin treatment modified metabolites involved in suppressing lipogenesis, oxidative stress, and neoplastic formation. In the relative fatty acid quantitation analysis of Ad-CM, aspirin diminished fatty acid contents of C16:1, C18:1, C18:2, C20:4, and C24:1. This study is the first to show that aspirin modifies the metabolomics and fatty acid composition of 3T3-L1 adipocytes and inhibits obesity-associated inflammation that contributes to obesity-related breast cancer cell growth and migration.

scholarly journals Hypermethylation of CCND2 in Lung and Breast Cancer Is a Potential Biomarker and Drug Target

2018 ◽  
Vol 19 (10) ◽  
pp. 3096 ◽  
Author(s):  
Chin-Sheng Hung ◽  
Sheng-Chao Wang ◽  
Yi-Ting Yen ◽  
Tzong-Huei Lee ◽  
Wu-Che Wen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Patients ◽  
Drug Target ◽  
Promoter Hypermethylation ◽  
Breast Cancer Patients ◽  
Cancer Cell Growth ◽  
Migration Ability ◽  
Cell Growth And Migration ◽  
And Migration

Lung and breast cancer are the leading causes of mortality in women worldwide. The discovery of molecular alterations that underlie these two cancers and corresponding drugs has contributed to precision medicine. We found that CCND2 is a common target in lung and breast cancer. Hypermethylation of the CCND2 gene was reported previously; however, no comprehensive study has investigated the clinical significance of CCND2 alterations and its applications and drug discovery. Genome-wide methylation and quantitative methylation-specific real-time polymerase chain reaction (PCR) showed CCND2 promoter hypermethylation in Taiwanese breast cancer patients. As compared with paired normal tissues and healthy individuals, CCND2 promoter hypermethylation was detected in 40.9% of breast tumors and 44.4% of plasma circulating cell-free DNA of patients. The western cohort of The Cancer Genome Atlas also demonstrated CCND2 promoter hypermethylation in female lung cancer, lung adenocarcinoma, and breast cancer patients and that CCND2 promoter hypermethylation is an independent poor prognostic factor. The cell model assay indicated that CCND2 expression inhibited cancer cell growth and migration ability. The demethylating agent antroquinonol D upregulated CCND2 expression, caused cell cycle arrest, and inhibited cancer cell growth and migration ability. In conclusion, hypermethylation of CCND2 is a potential diagnostic, prognostic marker and drug target, and it is induced by antroquinonol D.

scholarly journals Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi-Chun Cheng ◽  
Li-Yu Su ◽  
Li-Han Chen ◽  
Tzu-Pin Lu ◽  
Eric Y. Chuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Breast Cancer Progression ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Endogenous Expression ◽  
And Migration ◽  
Proliferation And Migration

Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under different oxygen concentrations. Among them, a novel mitochondria-encoded lncRNA, mitochondrial oxygen-responsive transcript 1 (MTORT1), was chosen for further investigation. Nuclear, cytoplasmic, and mitochondrial fractionation assays were performed to evaluate the endogenous expression levels of MTORT1 in breast cancer cells. In vitro proliferation and migration assays were conducted to investigate the functions of MTORT1 in breast cancer cells by knockdown of MTORT1. RNA immunoprecipitation and luciferase reporter assays were used to examine the physical binding between MTORT1 and microRNAs. Our results showed that MTORT1 had low endogenous expression levels in breast cancer cells and was mainly located in the mitochondria. Knockdown of MTORT1 enhanced cell proliferation and migration, implying a tumor suppressor role of this novel mitochondrial lncRNA. MTORT1 served as sponge of miR-26a-5p to up-regulate its target genes, CREB1 and STK4. Our findings shed some light on the characterization, function, and regulatory mechanism of the novel hypoxia-induced mitochondrial lncRNA MTORT1, which functions as a microRNA sponge and may inhibit breast cancer progression. These data suggest that MTORT1 may be a candidate for therapeutic targeting of breast cancer progression.

scholarly journals ARSD, a novel ERα downstream target gene, inhibits proliferation and migration of breast cancer cells via activating Hippo/YAP pathway

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Yun Lin ◽  
Chun Li ◽  
Wei Xiong ◽  
Liping Fan ◽  
Hongchao Pan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cpg Islands ◽  
Systematic Investigation ◽  
Good Prognosis ◽  
Hippo Signaling ◽  
Loop Formation ◽  
Downstream Target ◽  
Potential Marker ◽  
And Migration ◽  
Proliferation And Migration

AbstractAdvanced breast cancer (BC), especially basal like triple-negative BC (TNBC), is a highly malignant tumor without viable treatment option, highlighting the urgent need to seek novel therapeutic targets. Arylsulfatase D (ARSD), localized at Xp22.3, is a female-biased gene due to its escaping from X chromosome inactivation (XCI). Unfortunately, no systematic investigation of ARSD on BC has been reported. In this study, we observed that ARSD expression was positively related to ERα status either in BC cells or tissue specimens, which were associated with good prognosis. Furthermore, we found a set of hormone-responsive lineage-specific transcription factors, FOXA1, GATA3, ERα, directly drove high expression of ARSD through chromatin looping in luminal subtype BC cells. Opposingly, ARSD still subjected to XCI in TNBC cells mediated by Xist, CpG islands methylation, and inhibitory histone modification. Unexpectedly, we also found that ectopic ARSD overexpression could inhibit proliferation and migration of TNBC cells by activating Hippo/YAP pathway, indicating that ARSD may be a molecule brake on ERα signaling pathway, which restricted ERα to be an uncontrolled active status. Combined with other peoples’ researches that Hippo signaling maintained ER expression and ER + BC growth, we believed that there should exist a regulative feedback loop formation among ERα, ARSD, and Hippo/YAP pathway. Collectively, our findings will help filling the knowledge gap about the influence of ARSD on BC and providing evidence that ARSD may serve as a potential marker to predict prognosis and as a therapeutic target.

scholarly journals Macrophage conditioned media promotes adipocyte cancer-association, which in turn stimulates breast cancer proliferation and migration

2021 ◽  
Author(s):  
Dale B. Bosco ◽  
Yi Ren ◽  
Karin A. Vallega ◽  
Qing-Xiang Amy Sang
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Conditioned Media ◽  
Expression Levels ◽  
Cell Counts ◽  
And Migration ◽  
Promote Breast Cancer ◽  
Proliferation And Migration

Abstract Background Breast cancer is the most common cancer in women and the leading cause of female cancer deaths worldwide. Obesity causes chronic inflammation and is a risk factor for post-menopausal breast cancer and poor prognosis. Obesity triggers increased infiltration of macrophages into adipose tissue, yet little research has focused on the effects of macrophages in early stages of breast tumor development in obese patients. In this study, the effects of pro-inflammatory macrophages on breast cancer-adipocyte crosstalk were investigated.Methods An innovative human cell co-culture system was used to model the paracrine interactions among adipocytes, macrophages, and breast cancer cells, and how they facilitate tumor progression. The effects on cancer cells were examined using cell counts and migration assays. Quantitative reverse-transcription polymerase chain reaction was used to measure the expression levels of several cytokines and proteases to analyze adipocyte cancer-association.Results Macrophage conditioned media intensified the effects of breast cancer-adipocyte crosstalk. Adipocytes became delipidated and increased production of pro-inflammatory cytokines, even in the absence of cancer cells, although the expression levels were highest with all three cell components. As a result, co-cultured breast cancer cells became more aggressive, with increased proliferation and migration compared to adipocyte-breast cancer co-cultures treated with unconditioned media.Conclusions Macrophage conditioned media promotes adipocyte cancer-association. These macrophage-adipocyte paracrine interactions promote breast cancer cell proliferation and migration. Thus, macrophages may contribute to adipocyte inflammation and cancer-association and promote breast cancer progression.

scholarly journals OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression

Oncogenesis ◽  
2020 ◽  
Vol 9 (12) ◽  
Author(s):  
Mirco Masi ◽  
Enrico Garattini ◽  
Marco Bolis ◽  
Daniele Di Marino ◽  
Luisa Maraccani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Drug Target ◽  
Cell Proliferation And Migration ◽  
Membrane Bound ◽  
And Migration ◽  
Androgen Effects ◽  
Proliferation And Migration

AbstractRecent data indicate that receptor for activated C kinase 1 (RACK1) is a putative prognostic marker and drug target in breast cancer (BC). High RACK1 expression is negatively associated with overall survival, as it seems to promote BC progression. In tumors, RACK1 expression is controlled by a complex balance between glucocorticoids and androgens. Given the fact that androgens and androgenic derivatives can inhibit BC cell proliferation and migration, the role of androgen signaling in regulating RACK1 transcription in mammary tumors is of pivotal interest. Here, we provide evidence that nandrolone (19-nortosterone) inhibits BC cell proliferation and migration by antagonizing the PI3K/Akt/NF-κB signaling pathway, which eventually results in RACK1 downregulation. We also show that nandrolone impairs the PI3K/Akt/NF-κB signaling pathway and decreases RACK1 expression via binding to the membrane-bound receptor, oxoeicosanoid receptor 1 (OXER1). High levels of OXER1 are observed in several BC cell lines and correlate with RACK1 expression and poor prognosis. Our data provide evidence on the role played by the OXER1-dependent intracellular pathway in BC progression and shed light on the mechanisms underlying membrane-dependent androgen effects on RACK1 regulation. Besides the mechanistic relevance, the results of the study are of interest from a translational prospective. In fact, they identify a new and actionable pathway to be used for the design of innovative and rational therapeutic strategies in the context of the personalized treatment of BC. In addition, they draw attention on nandrolone-based compounds that lack hormonal activity as potential anti-tumor agents.

scholarly journals Hsa_circ_0005273 regulates YAP1-Hippo signaling pathway by targeting miR-200a-3p to promote breast cancer progression.

2020 ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Qifeng Luo ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background : Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functions of hsa_circ_0005273 in breast cancer remains unknown. Here we aim to explore the role of hsa_circ_0005273 in BC. Methods : We chose miR-200a-3p as the potential target of hsa_circ_0005273. The expression levels of hsa_circ_0005273 and miR-200a-3p were examined in BC tissues compared with adjacent normal tissues by qRT-PCR. To characterize the function of hsa_circ_0005273, experiments of cell proliferation and migration were performed in BC cell lines infected with lentivirus targeting hsa_circ_0005273. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. Luciferase reporter assay was conducted to confirm the relationship between hsa_circ_0005273 and miR-200a-3p as well as miR-200a-3p andYAP1. Results : Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of has_circ_0005273 or upregulation of miR-200a-3p inhibited the proliferation and migration of BC cells in vitro and vivo. Mechanistically, hsa_circ_0005273 upregulated YAP1 by targeting miR-200a-3p and activated Hippo signaling pathway to promote BC progression. Conclusions : Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and activates Hippo signaling pathway to promote BC progression, and it may serve as a potential biomarker and therapeutic target. Keywords : breast cancer, hsa_circ_0005273, miR-200a-3p,YAP1, progression

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