scholarly journals MicroRNA let-7g directly targets forkhead box C2 (FOXC2) to modulate bone metastasis in breast cancer

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Lei Wang ◽  
Ming Li ◽  
Yongxin Zhou ◽  
Yu Zhao
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Bone Metastasis ◽  
Western Blot ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Qrt Pcr ◽  
Forkhead Box ◽  
Novel Target ◽  
Cancer Tissues

AbstractAberrantly expressed microRNAs have been implicated in lots of cancers. Reduced amounts of let-7g have been found in breast cancer tissues. The function of let-7g in bone metastasis of breast cancer remains poorly understood. This study is to explore the significance of let-7g and its novel target gene in bone metastasis of breast cancer.The expression of let-7g or forkhead box C2 (FOXC2) was measured in human clinical breast cancer tissues with bone metastasis by using quantitative real-time Polymerase Chain Reaction (qRT-PCR). After transfection with let-7g or anti-let-7g in breast cancer cell linesMDA-MB-231or SK-BR3, qRT-PCR and Western blot were done to test the levels of let-7g and FOXC2. The effect of anti-let-7g and/ or FOXC2 RNA interference (RNAi) on cell migration in breast cancer cells was evaluated by using wound healing assay.Clinically, qRT-PCR showed that FOXC2 levels were higher in breast cancer tissues with bone metastasis than those in their noncancerous counterparts. Let-7g was showed to be negatively correlated with FOXC2 in human breast cancer samples with bone metastasis. We found that enforced expression of let-7g reduced levels of FOXC2 protein by using Western blot in MDA-MB-231 cells. Conversely, anti-let-7g enhanced levels of FOXC2 in SK-BR3 cells. In terms of function, anti-let-7g accelerated migration of SK-BR3 cells. Interestingly, FOXC2 RNAi abrogated anti-let-7g-mediated migration in breast cancer cells. Thus, we conclude that let-7g suppresses cell migration through targeting FOXC2 in breast cancer. Our finding provides a new perspective for understanding the mechanism of bone metastasis in breast cancer.

scholarly journals ATP Inhibits Breast Cancer Migration and Bone Metastasis through Down-Regulation of CXCR4 and Purinergic Receptor P2Y11

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4293
Author(s):  
Xiaowen Liu ◽  
Manuel A. Riquelme ◽  
Yi Tian ◽  
Dezhi Zhao ◽  
Francisca M. Acosta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cxcr4 Expression ◽  
Dependent Manner ◽  
Cancer Cell Migration ◽  
Dose Dependent

ATP released by bone osteocytes is shown to activate purinergic signaling and inhibit the metastasis of breast cancer cells into the bone. However, the underlying molecular mechanism is not well understood. Here, we demonstrate the important roles of the CXCR4 and P2Y11 purinergic receptors in mediating the inhibitory effect of ATP on breast cancer cell migration and bone metastasis. Wound-healing and transwell migration assays showed that non-hydrolysable ATP analogue, ATPγS, inhibited migration of bone-tropic human breast cancer cells in a dose-dependent manner. BzATP, an agonist for P2X7 and an inducer for P2Y11 internalization, had a similar dose-dependent inhibition on cell migration. Both ATPγS and BzATP suppressed the expression of CXCR4, a chemokine receptor known to promote breast cancer bone metastasis, and knocking down CXCR4 expression by siRNA attenuated the inhibitory effect of ATPγS on cancer cell migration. While a P2X7 antagonist A804598 had no effect on the impact of ATPγS on cell migration, antagonizing P2Y11 by NF157 ablated the effect of ATPγS. Moreover, the reduction in P2Y11 expression by siRNA decreased cancer cell migration and abolished the impact of ATPγS on cell migration and CXCR4 expression. Similar to the effect of ATPγS on cell migration, antagonizing P2Y11 inhibited bone-tropic breast cancer cell migration in a dose-dependent manner. An in vivo study using an intratibial bone metastatic model showed that ATPγS inhibited breast cancer growth in the bone. Taken together, these results suggest that ATP inhibits bone-tropic breast cancer cells by down-regulating the P2Y11 purinergic receptor and the down-regulation of CXCR4 expression.

scholarly journals MiR-9-3p regulates the biological functions and drug resistance of gemcitabine-treated breast cancer cells and affects tumor growth through targeting MTDH

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yike Wang ◽  
Lifeng Dong ◽  
Fang Wan ◽  
Fangfang Chen ◽  
Dianlei Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Biological Functions ◽  
Qrt Pcr ◽  
Treated Breast ◽  
Cancer Tissues ◽  
Treated Breast Cancer

AbstractThis study explored the role of MTDH in regulating the sensitivity of breast cancer cell lines to gemcitabine (Gem) and the potential miRNAs targeting MTDH. The expression of MTDH in cancer tissues and cells was detected by immunohistochemical staining or qRT-PCR. The target genes for MTDH were predicted by bioinformatics and further confirmed by dual-luciferase reporter assay and qRT-PCR. Cancer cells were transfected with siMTDH, MTDH, miR-9-3p inhibitor, or mimics and treated by Gem, then CCK-8, colony formation assay, tube formation assay, flow cytometry, wound healing assay, and Transwell were performed to explore the effects of MTDH, miR-9-3p, and Gem on cancer cell growth, apoptosis, migration, and invasion. Expressions of VEGF, p53, cleaved caspase-3, MMP-2, MMP-9, E-Cadherin, N-Cadherin, and Vimentin were determined by Western blot. MTDH was high-expressed in cancer tissues and cells, and the cells with high-expressed MTDH were less sensitive to Gem, while silencing MTDH expression significantly promoted the effect of Gem on inducing apoptosis, inhibiting cell migration, invasion, and growth, and on regulating protein expressions of cancer cells. Moreover, miR-9-3p had a targeted binding relationship with MTDH, and overexpressed miR-9-3p greatly promoted the toxic effects of Gem on cancer cells and expressions of apoptosis-related proteins, whereas overexpressed MTDH partially reversed such effects of overexpressed miR-9-3p. The study proved that miR-9-3p regulates biological functions, drug resistance, and the growth of Gem-treated breast cancer cells through targeting MTDH.

BRMS1L inhibits bone metastasis of breast cancer cells through epigenetic silence of CXCR4.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13002-e13002
Author(s):  
Yinghuan Cen ◽  
Chang Gong ◽  
Jun Li ◽  
Gehao Liang ◽  
Zihao Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Qrt Pcr ◽  
Metastatic Sites

e13002 Background: We previously demonstrated that BRMS1L (breast cancer metastasis suppressor 1 like) suppresses breast cancer metastasis through HDAC1 recruitment and histone H3K9 deacetylation at the promoter of FZD10, a receptor for Wnt signaling. It is still unclear whether BRMS1L regulates organ-specific metastases, such as bone metastasis, the most prevalent metastatic site of breast cancer. Methods: Examination of the expression of BRMS1L in primary tumors, bone metastatic and other metastatic tissues from breast cancer patients was implemented using qRT-PCR and immunohistochemistry staining. To investigate the mechanism by which BRMS1L drives breast cancer bone metastasis, we tested the mRNA expression by qRT-PCR of a set of potential bone related genes (BRGs) based on PubMed database in MDA-MB-231 cells over expressing BRMS1L and MCF-7 cells knocking-down BRMS1L, and detected the expression of CXCR4 in these established cells by western blot. Transwell assays were performed to assess the migration abilities of breast cancer cells towards osteoblasts. ChIP (Chromatin Immuno-Precipitation) were employed to test the interaction between BRMS1L and CXCR4. Results: At both mRNA and protein levels, the expression of BRMS1L was significantly lower in bone metastatic sites than that in primary cancer tissues and other metastatic sites of breast cancer patients. CXCR4 was screened out in a set of BRGs and negatively correlated with the expression of BRMS1L in breast cancer cell lines. BRMS1L inhibited the migration of breast cancer cells towards osteoblasts through CXCL12/CXCR4 axis. In the presence of TSA treatment, breast cancer cell lines showed an increased expression of CXCR4 in a TSA concentration-dependent manner. In addition, ChIP assays verified that BRMS1L directly bound to the promoter region of CXCR4 and inhibited its transcription through promoter histone deacetylation. Conclusions: BRMS1L mediates the migration abilities of breast cancer cells to bone microenvironment via targeting CXCR4 and contributes to bone metastasis of breast cancer cells. Thus, BRMS1L may be a potential biomarker for predicting bone metastasis in breast cancer.

scholarly journals New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Zhang ◽  
Xiaofeng Huang ◽  
Jin Liu ◽  
Guo Chen ◽  
Chengjun Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastasis ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Lung Metastasis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Qrt Pcr ◽  
Non Coding Rnas

Abstract Background Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer. Methods Four mRNA datasets and two lncRNA datasets of bone metastasis, lung metastasis and liver metastasis of breast cancer were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, as well as the overlap of the two groups, were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein–protein interaction (PPI) network construction of DEmRNAs were conducted. The cis nearby-targeted DEmRNAs of DElncRNAs were obtained. Quantitative real-time polymerase chain reactions (qRT-PCR) was used to detect the expression levels of selected DEmRNAs and DElncRNAs. LOC641518-lymphoid enhancer-binding factor 1 (LEF1) pair was selected to verify its role in migration and invasion capability of breast cancer cells by wounding healing assay and transwell invasion assay. Results A total of 237 DEmRNAs were obtained in bone metastasis compared with both lung metastasis and liver metastasis. A total of three DElncRNAs in bone metastasis compared with both lung metastasis and liver metastasis were obtained. A total of seven DElncRNA-nearby-targeted DEmRNA pairs and 15 DElncRNA-nearby-targeted DEmRNA pairs in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, were detected, respectively. Four cis LncRNA-mRNA interaction pairs were identified, which are LOC641518-LEF1, FLJ35024-Very Low Density Lipoprotein Receptor (VLDLR), LOC285972-Retinoic Acid Receptor Responder 2 (RARRES2) and LOC254896-TNF receptor superfamily member 10c (TNFRSF10C). qRT-PCR using clinical samples from our hospital confirms the bioinformatics prediction. siRNA knocking down LOC641518 down-regulates LEF1 mRNA expression, and reduces the migration and invasion capability of breast cancer cells. Conclusions We concluded that four LncRNA-mRNA pairs, including LOC641518-LEF1, may play a central role in breast cancer bone metastasis.

scholarly journals miR-17-5p Combined with Epirubicin Inhibits the Progression of Breast Cancer Cells

2020 ◽  
Author(s):  
Lingling Zhao ◽  
Zhongjian Zhu ◽  
Jiang Du ◽  
Yuanyu Zhao ◽  
Dandan Fan
Keyword(s):  
Breast Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Rt Pcr ◽  
Expression Levels ◽  
Cancer Tissues ◽  
Mcf 7

Abstract Background: Breast cancer is the most common malignant tumor for women, which has been ranked first in women’ s cancer-related death. The objectives of the study are to uncover the underlying mechanisms of combination therapy of epirubicin with miR-17-5p in breast cancer. Methods: The expression levels of miR-17-5p were determined by quantitative RT-PCR. The survival rate of MCF-7 cell was detected respectively by MTT assay. The expression levels of miR-17-5p in MCF-7 cell was tested respectively with Ep via quantitative RT-PCR. miR-17-5p was to be transected with miR-17-5p mimic and negative control of miR-17-5p mimic (NC). Quantitative RT-PCR, MTT assay, flow cytometry assay, western blot for the proliferation and apoptosis related proteins were performed to determine the function of miR-17-5p in breast cancer cells. The bioinformatic programs TargetScan was used to predict the targets for miR-17-5p. Luciferase reporter gene assay system was used to validate and determine the targets of miR-17-5p. The relation between targets protein levels in breast cancer cells was investigated by western blot. Results: The expression levels of miR-17-5p was associated with the breast cancer tissues. The levels of miR-17-5p was down-regulated in breast cancer tissues and cells. Ep could inhibit viability of cancer cells in a concentration dependent manner and promote the expression of miR-17-5p in breast cancer cell lines. Over-expression of miR-17-5p induced cell apoptosis and upregulated the expression of p53, p21 and p27. miR-17-5p co-cultured with Ep is better than the other groups. The relative luciferase activity revealed that STAT3 was a potential target gene of miR-17-5p. Conclusions: Our work will prove that epirubicin regulated the expression of miR-17-5p to strengthen this effect of epirubicin and inhibited the progression of breast cancer.

scholarly journals Circular RNA circCCDC85A inhibits breast cancer progression via acting as a miR-550a-5p sponge to enhance MOB1A expression

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Lingjiao Meng ◽  
Sheng Chang ◽  
Yang Sang ◽  
Pingan Ding ◽  
Liuxin Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Breast Cancer Progression ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Qrt Pcr ◽  
Cancer Tissues

Abstract Background A growing body of evidence indicates that abnormal expression of circular RNAs (circRNAs) plays a crucial role by acting as molecular sponges of microRNAs (miRNAs) in various diseases, including cancer. In this study, we explored whether circCCDC85A could function as a miR-550a-5p sponge and influence breast cancer progression. Methods We detected the expression of circCCDC85A in breast cancer tissues and cells using fluorescence in situ hybridization (FISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). CCK-8 and colony formation assay were used to detect the proliferative ability of breast cancer cells. Wound healing assay and transwell migration and invasion assays were used to detect the migrative and invasive abilities of breast cancer cells. We also examined the interactions between circCCDC85A and miR-550a-5p using FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Moreover, we performed luciferase reporter assay, qRT-PCR, and Western blot to confirm the direct targeting of miR-550a-5p to MOB1A. Results The expression of circCCDC85A in breast cancer tissues was obviously lower than that in normal breast tissues. Over-expression of circCCDC85A substantially inhibited the proliferative, migrative, and invasive ability of breast cancer cells, while knocking down of circCCDC85A enhanced the aforementioned properties of breast cancer cells. Moreover, enforced expression of circCCDC85A inhibits the oncogenic activity of miR-550a-5p and increases the expression of MOB1A targeted by miR-550a-5p. Further molecular mechanism research showed that circCCDC85A may act as a molecular sponge for miR-550a-5p, thus restoring miR-550a-5p-mediated targeting repression of tumor suppressor MOB1A in breast cancer cells. Conclusion Our findings provide novel evidence that circCCDC85A inhibits the progression of breast cancer by functioning as a molecular sponge of miR-550a-5p to enhance MOB1A expression.

scholarly journals Silencing of SOX12 by shRNA suppresses migration, invasion and proliferation of breast cancer cells

2016 ◽  
Vol 36 (5) ◽  
Author(s):  
Hanzhi Ding ◽  
Hong Quan ◽  
Weiguo Yan ◽  
Jing Han
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast ◽  
Cancer Tissues

SOX12 mRNA expression was up-regulated in human breast cancer tissues. SOX12 was critical for cell migration, invasion and proliferation of breast cancer cells.

Docking Protein 2 Inhibits Proliferation, Migration and Invasion of Breast Cancer Cells via the Ras/Extracellular Regulated Protein Kinases Pathway

2020 ◽  
Vol 10 (5) ◽  
pp. 690-697
Author(s):  
Yongmei Zhang ◽  
Huayi Zhang ◽  
Gang Guo ◽  
Xiping Zhang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Western Blot ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Erk Pathway ◽  
Related Proteins ◽  
Docking Protein

Background: This study was designed to investigate the effects of Downstream of Tyrosine Kinase 2, Docking Protein 2 (DOK2) on breast cancer cells, and its potential mechanism in disease pathogenesis. Methods: The expression of DOK2 in human breast cancer cell lines and mammary epithelial cells were assessed by RT-qPCR and Western blot assay. CCK8 was used to evaluate cell proliferation, wound healing and transwell were used to detect cell migration and invasion. Furthermore, Western blot was used to detect the expression of migration-related proteins, MMP2, MMP9 and Ras/ERK pathway-related proteins. Results: The expression level of DOK2 was significantly lower in breast cancer MCF7 and MDA-MB-231 cells compared with the normal breast cancer cell line MCF10A. To further investigate the function of DOK2, the overexpressed plasmid of DOK2 was transfected into MCF7 and MDA-MB-231 cells, the results revealed that DOK2 markedly inhibited cell proliferation, cell migration and invasion via inhibiting the Ras/ERK pathway. Conclusions: Collectively, the data demonstrated that DOK2 could directly inhibits proliferation, migration and invasion of breast cancers via inhibiting the Ras/ERK pathway.

New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis

2021 ◽  
Author(s):  
Yu zhang ◽  
Xiaofeng Huang ◽  
Jin Liu ◽  
Guo Chen ◽  
Chengjun Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastasis ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Lung Metastasis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Qrt Pcr ◽  
Non Coding Rnas

Abstract Background Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer. Methods Four mRNA datasets and two lncRNA datasets of bone metastasis, lung metastasis and liver metastasis of breast cancer were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, as well as the overlap of the two groups, were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network construction of DEmRNAs were conducted. The cis nearby-targeted DEmRNAs of DElncRNAs were obtained. Quantitative real-time polymerase chain reactions (qRT-PCR) was used to detect the expression levels of selected DEmRNAs and DElncRNAs. LOC641518- lymphoid enhancer-binding factor 1 (LEF1) pair was selected to verify its role in migration and invasion capability of breast cancer cells by wounding healing assay and transwell invasion assay. Results A total of 237 DEmRNAs were obtained in bone metastasis compared with both lung metastasis and liver metastasis. A total of 3 DElncRNAs in bone metastasis compared with both lung metastasis and liver metastasis were obtained. A total of 7 DElncRNA-nearby-targeted DEmRNA pairs and 15 DElncRNA-nearby-targeted DEmRNA pairs in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, were detected, respectively. Four cis LncRNA-mRNA interaction pairs were identified, which are LOC641518-LEF1, FLJ35024-Very Low Density Lipoprotein Receptor (VLDLR), LOC285972-Retinoic Acid Receptor Responder 2 (RARRES2) and LOC254896- TNF receptor superfamily member 10c (TNFRSF10C). qRT-PCR using clinical samples from our hospital confirms the bioinformatics prediction. siRNA knocking down LOC641518 down-regulates LEF1 mRNA expression, and reduces the migration and invasion capability of breast cancer cells. Conclusions We concluded that four LncRNA-mRNA pairs, including LEF1-AS1-LEF1, may play a central role in breast cancer bone metastasis.

Sign in / Sign up

Export Citation Format

Share Document