The roles of microRNA-328-3p on proliferation and radiotherapy in breast cancer

2021 ◽  
Author(s):  
Ying Shi ◽  
Pengli Jiang ◽  
Jinqiu Li ◽  
Shengnan Xu ◽  
Bin Liu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Breast Carcinogenesis ◽  
Aberrant Expression ◽  
Induced Apoptosis ◽  
Cancer Tissues ◽  
The Impact

Abstract Objectives MicroRNAs regulates varieties of molecular pathways and involve in breast carcinogenesis. Here both breast cancer cell lines and human breast cancer tissues were used to investigate the roles of miR-328-3p in breast cancer. Methods The impact of miR-328-3p on proliferation of MDA-MB-231 and T47D cells was determined by MTT assay. transwell migration and matrigel invasion assays were performed to evaluate effects of miR-328-3p on migration and invasion of breast cancer cells. Caspase 3/7 activities were measured to examine the impact of miR-328-3p on radiotherapy-induced apoptosis in breast cancer cells. The possible binding site of miR-328-3p was verified by dual-luciferase reporter assay. Quantitative real-time polymerase chain reaction was performed to detect miR-328-3p expression level in breast cancer tissues. Western blot and immunohistochemical studies were used to examine protein expression in breast cancer cells and breast cancer tissue, respectively. Results miR-328-3p involved growth, migration and invasion in breast cancer cells and was associated with radiotherapy sensitivity. MiR-328-3p enhanced radiation-induced apoptosis in breast cancer cells by regulating BAX and Bcl-2 expression. Meanwhile, aberrant expression of miR-328-3p was associated with altered expression of PTEN and p-AKT in breast cancer cells. Further study showed miR-328-3p bound to 3’-UTR of PTEN. In addition, breast cancer tissues showed higher level of miR-328-3p than normal breast tissue and higher level of miR-328-3p was seen in lower stage in breast cancer. Conclusions miR-328-3p displayed essential functions in breast carcinogenesis and might be used to predict radiotherapy response and prognosis in breast cancer.

ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

2021 ◽  
pp. 096032712198942
Author(s):  
Xiaoxue Zhang ◽  
Xianxin Xie ◽  
Kuiran Gao ◽  
Xiaoming Wu ◽  
Yanwei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

scholarly journals ΕGFR/ERβ-Mediated Cell Morphology and Invasion Capacity Are Associated with Matrix Culture Substrates in Breast Cancer

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2256
Author(s):  
Konstantina Kyriakopoulou ◽  
Eirini Riti ◽  
Zoi Piperigkou ◽  
Konstantina Koutroumanou Sarri ◽  
Heba Bassiony ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Morphology ◽  
Breast Cancer Cells ◽  
Type I Collagen ◽  
Morphological Characteristics ◽  
Migration And Invasion ◽  
Type I ◽  
Egfr Inhibition ◽  
The Impact

Breast cancer accounts for almost one in four cancer diagnoses in women. Studies in breast cancer patients have identified several molecular markers, indicators of aggressiveness, which help toward more individual therapeutic approaches. In triple-negative breast cancer (TNBC), epidermal growth factor receptor (EGFR) overexpression is associated with increased metastatic potential and worst survival rates. Specifically, abnormal EGFR activation leads to altered matrix metalloproteinases’ (MMPs) expression and, hence, extracellular matrix (ECM) degradation, resulting in induced migration and invasion. The use of matrix substrates for cell culture gives the opportunity to mimic the natural growth conditions of the cells and their microenvironment, as well as cell–cell and cell–matrix interactions. The aim of this study was to evaluate the impact of EGFR inhibition, estrogen receptor beta (ERβ) and different matrix substrates [type I collagen and fibronectin (FN)] on the functional properties, expression of MMPs and cell morphology of ERβ-positive TNBC cells and shERβ ones. Our results highlight EGFR as a crucial regulator of the expression and activity levels of MMPs, while ERβ emerges as a mediator of MMP7 and MT1-MMP expression. In addition, the EGFR/ERβ axis impacts the adhesion and invasion potential of breast cancer cells on collagen type I. Images obtained by scanning electron microscope (SEM) from cultures on the different matrix substrates revealed novel observations regarding various structures of breast cancer cells (filopodia, extravesicles, tunneling nanotubes, etc.). Moreover, the significant contribution of EGFR and ERβ in the morphological characteristics of these cells is also demonstrated, hence highlighting the possibility of dual pharmacological targeting.

LncRNA NEAT1 accelerates breast cancer progression through regulating miR-410-3p/ CCND1 axis

2020 ◽  
Vol 29 (2) ◽  
pp. 277-290
Author(s):  
Xuan Liu ◽  
Weirong Yao ◽  
Haiwei Xiong ◽  
Qiang Li ◽  
Yingliang Li
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Breast Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Cancer Tissues

BACKGROUND: Breast cancer is the most common malignant tumor and usually occurs in women. Studies have shown that lncRNA nuclear enriched abundant transcript 1 (NEAT1) contributes to breast cancer progression. This study intends to further investigate the molecular mechanism of NEAT1 in breast cancer. METHODS: The expression levels of NEAT1, miR-410-3p and Cyclin D1 (CCND1) were detected by quantitative real-time PCR (qRT-PCR) in breast cancer tissues and cells. Kaplan-Meier analysis and the log-rank test were performed to determine the relationship between NEAT1 and overall survival. Cell Counting Kit-8 (CCK-8) assay analyzed cell proliferation. Transwell assay was performed to examine cell migration and invasion. The protein levels of CCND1 and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin) were measured by western blot. The target relationship was predicted by bioinformatics analysis, and confirmed by luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. Xenograft analysis was used to evaluate the tumor growth in vivo. RESULTS: NEAT1 and CCND1 were upregulated, while miR-410-3p was down-regulated in breast cancer tissues and cells. Higher NEAT1 expression level was associated with lower survival rate of breast cancer patients. Knockdown of miR-410-3p restored silenced NEAT1-mediated the inhibition of on proliferation, migration, invasion and EMT of breast cancer cells. In addition, NEAT1 regulated CCND1 expression by sponging miR-410-3p in breast cancer cells. NEAT1 knockdown blocked the tumor growth in vivo. CONCLUSION: NEAT1 induced breast cancer progression by regulating the miR-410-3p/CCND1 axis, indicating that NEAT1 may be a potential therapeutic target in breast cancer.

scholarly journals hsa-miR-33-5p as a Therapeutic Target Promotes Apoptosis of Breast Cancer Cells via Selenoprotein T

2021 ◽  
Vol 8 ◽  
Author(s):  
Wei Zhuang ◽  
Jianhui Liu ◽  
Wenjin Li
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Selenoprotein T ◽  
Cancer Tissues ◽  
Mcf 7

Objective: Increasing evidence suggests that microRNA (miRNA) participates in regulating tumor cell apoptosis. We aimed to observe the effect of hsa-miR-33-5p on the apoptosis of breast cancer cells and to explore its regulatory relationship with selenoprotein T (SelT).Methods: RT-qPCR was used to examine the expression of hsa-miR-33-5p and SelT both in breast cancer tissues and cells. MCF-7 and MDA-MB-231 cells were transfected with hsa-miR-33-5p mimics or si-SelT. Then, a flow cytometry assay was carried out to examine the apoptosis of cells. Furthermore, SelT and apoptosis-related proteins including caspase-3, caspase-8, caspase-9, Bax, and Bcl-2 were detected via RT-qPCR and western blot. A luciferase reporter assay was utilized for assessing whether SelT was targeted by hsa-miR-33-5p.Results: Downregulated hsa-miR-33-5p was found both in breast cancer tissues and cells. After its overexpression, MCF-7 cell apoptosis was significantly promoted. Furthermore, our data showed that miR-33-5p elevated apoptosis-related protein expression in MCF-7 cells. Contrary to hsa-miR-33-5p, SelT was upregulated both in breast cancer tissues and cells. SelT expression was significantly inhibited by hsa-miR-33-5p overexpression. The luciferase reporter assay confirmed that SelT was a direct target of hsa-miR-33-5p. SelT overexpression could ameliorate the increase in apoptosis induced by hsa-miR-33-5p mimics.Conclusion: Our findings revealed that hsa-miR-33-5p, as a potential therapeutic target, could accelerate breast cancer cell apoptosis.

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

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.

scholarly journals Shikonin inhibits migration and invasion of triple-negative breast cancer cells by suppressing epithelial-mesenchymal transition via miR-17-5p/PTEN/Akt pathway

2020 ◽  
Author(s):  
Chang Bao ◽  
Tao Liu ◽  
Lingbo Qian ◽  
Chi Xiao ◽  
Xinru Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Pathway Enrichment Analysis ◽  
Mesenchymal Transition

Abstract Background: Triple-negative breast cancer(TNBC) is a great threat to global women’s health due to its high metastatic potential. Epithelial-to-mesenchymal transition (EMT) is considered as a key event in the process of metastasis. So the pharmacological targeting of EMT might be a promising strategy in improving the therapeutic efficacy of TNBC. Here, we investigated the effect of shikonin exerting on EMT and consequently the metastasis of TNBC cells and its underlying mechanism.Methods: The invasive and migratory capacities of MDA-MB-231 cells were tested using transwell invasion and wound healing assay. MiR-17-5p expression was examined by qRT-PCR. MiR-17-5p targeted genes were predicted with different bioinformatic algorithms from four databases (TargetScan, miRanda, PITA and picTar) and further screened by KEGG pathway enrichment analysis. The differential expressions of predicted genes and their correlations with miR-17-5p were identifed in breast cancer patients based on The Cancer Genome Atlas (TCGA) database. The interaction between PTEN and miR-17-5p was analyzed by luciferase reporter assay. The overexpression vector and small interfering RNA were constructed to investigate the role PTEN played in matastasis and EMT regulation. The expressions of EMT markers, Akt and p-Akt were evaluated by western blot.Results: Shikonin inhibited the migration and invasion of MDA-MB-231 cells by suppressing EMT. Shikonin suppressed the expression of miR-17-5p, which was upregulated in breast cancer and promoted cancer cell migration, invasion and EMT. The 3’-untranslated region of PTEN was found to be direct binding target of miR-17-5p. PTEN expression increased or decreased in breast cancer cells transfected with miR-17-5p inhibitors or mimics respectively. PTEN functioned as a suppressor both in the metastasis and EMT of TNBC cells. Overexpression or knockdown of PTEN reduced or increased the Akt and p-Akt expression respectively.Conclusions: Shikonin inhibits migration and invasion of TNBC cells by suppressing EMT via miR-17-5p/PTEN/Akt pathway. This suggests shikonin as a promising therapeutic agent to counteract metastasis in the TNBC patients.

scholarly journals Echinacoside Suppresses the Progression of Breast Cancer by Downregulating the Expression of miR-4306 and miR-4508

2021 ◽  
Vol 20 ◽  
pp. 153473542110626
Author(s):  
Peng Bian ◽  
Chuan Liu ◽  
Wei Hu ◽  
Yu Ding ◽  
Shusheng Qiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effect ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Anticancer Effects ◽  
And Migration ◽  
Cancer Tissues

The main treatment of breast cancer includes surgical resection, radiotherapy, chemotherapy, endocrine therapy, and molecular targeted therapy, but the outcomes remain unsatisfactory. Previous studies demonstrated that echinacoside, microRNA (miRNA/miR)-4306 and miR-4508 were associated with lymph node metastasis, chemoresistance and self-renewal capability in breast cancer, but in-depth studies on the underlying mechanism of their anticancer effects have not been performed to date. In order to identify the role of miR-4306 and miR-4508, and the mechanism of the antitumor effect of echinacoside in breast cancer, the present study first examined the expression of miR-4306 and miR-4508 in breast cancer tissues to examine their possible role in the development of breast cancer, then evaluated the effect of echinacoside on the expression of miR-4306 and miR-4508 on the viability, apoptosis, cell cycle, migration, and invasion abilities of breast cancer cells to explore the anti-cancer effect of echinacoside and the involvement of miR-4306 and miR-4508. Finally, the breast cancer cells and mice bearing breast cancer xenografts were treated with echinacoside and inhibitors of miR-4508 or miR-4306 to confirm their role on the anticancer effect of echinacoside. The results showed that miR-4306 and miR-4508 were decreased in breast cancer tissues and cells. Echinacoside inhibited cell proliferation, invasion and migration, and promoted the apoptosis of breast cancer cells by downregulating the expression of miR-4306 and miR-4508. In conclusion, this is the first study to show the association between echinacoside and miRNAs in cancer. The present study elucidates an underlying molecular mechanism of the antitumor effect of echinacoside on breast cancer, and thus may contribute to preventive and therapeutic strategies for breast cancer.

MiR-539 inhibits the malignant behavior of breast cancer cells by targeting SP1

2020 ◽  
Vol 98 (3) ◽  
pp. 426-433 ◽  
Author(s):  
Fenglin Cai ◽  
Luhong Chen ◽  
Yuting Sun ◽  
Chunlan He ◽  
Deyuan Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Promising Target ◽  
Specificity Protein ◽  
Cancer Tissues

The aberrant expression of microRNAs (miRNAs) is involved in the initiation and progression of human cancers. In our study, we found that miR-539 was down-regulated in breast cancer tissues and cell lines. Decreased expression of miR-539 was significantly associated with lymph node metastasis in patients with breast cancer. Overexpression of miR-539 inhibited the proliferation and promoted apoptosis of breast cancer cells. Moreover, highly expressed miR-539 significantly suppressed the epithelial–mesenchymal transition (EMT) and sensitized cells to cisplatin treatment. Mechanistically, miR-539 was found to target the specificity protein 1 (SP1) and down-regulated the expression of SP1 in breast cancer cells. Knockdown of miR-539 consistently increased the expression of SP1. The expression of miR-539 in breast cancer tissues was negatively correlated with the expression of SP1. Restoration of SP1 significantly attenuated the inhibitory effect of miR-539 on the proliferation of breast cancer cells. Taken together, our results indicate that miR-539 has a tumor suppressive role in breast cancer via targeting SP1, suggesting miR-539 as a promising target for the diagnosis of breast cancer.

scholarly journals Atractylenolide-I Suppresses Tumorigenesis of Breast Cancer by Inhibiting Toll-Like Receptor 4-Mediated Nuclear Factor-κB Signaling Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Fangyi Long ◽  
Hong Lin ◽  
Xiqian Zhang ◽  
Jianhui Zhang ◽  
Hongtao Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Atractylenolide I ◽  
Cancer Tissues

Background: Toll-like receptor 4 (TLR4) is an essential sensor related to tumorigenesis, and overexpression of TLR4 in human tumors often correlates with poor prognosis. Atractylenolide‐I (AT-I), a novel TLR4-antagonizing agent, is a major bioactive component from Rhizoma Atractylodes Macrocephalae. Emerging evidence suggests that AT-I exerts anti-tumor effects on various cancers such as colorectal cancer, bladder cancer and melanoma. Nevertheless, the effects of AT-I on mammary tumorigenesis remain unclear.Methods: In order to ascertain the correlation of TLR4/NF-κB pathway with breast cancer, the expression of TLR4 and NF-κB in normal breast tissues and cancer tissues with different TNM-stages was detected by human tissue microarray and immunohistochemistry technology. The effects of AT-I on tumorigenesis were investigated by cell viability, colony formation, apoptosis, migration and invasion assays in two breast cancer cells (MCF-7 and MDA-MB-231), and N-Nitroso-N-methylurea induced rat breast cancer models were developed to evaluate the anti-tumor effects of AT-I in vivo. The possible underlying mechanisms were further explored by western blot and ELISA assays after a series of LPS treatment and TLR4 knockdown experiments.Results: We found that TLR4 and NF-κB were significantly up-regulated in breast cancer tissues, and was correlated with advanced TNM-stages. AT-I could inhibit TLR4 mediated NF-κB signaling pathway and decrease NF-κB-regulated cytokines in breast cancer cells, thus inhibiting cell proliferation, migration and invasion, and inducing apoptosis of breast cancer cells. Furthermore, AT-I could inhibit N-Nitroso-N-methylurea-induced rat mammary tumor progression through TLR4/NF-κB pathway.Conclusion: Our findings demonstrated that TLR4 and NF-κB were over expressed in breast cancer, and AT-I could suppress tumorigenesis of breast cancer via inhibiting TLR4-mediated NF-κB signaling pathway.

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