scholarly journals PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Li Zhu ◽  
Yan-Jun Zhang ◽  
Bin Wang ◽  
Li Yang ◽  
Yi-Qiong Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Feedback Loop ◽  
Tube Formation ◽  
Migration And Invasion ◽  
Common Life ◽  
Normal Tissues ◽  
Mechanistic Investigation ◽  
Direct Target Gene ◽  
Life Threatening ◽  
Cancer Tissues

Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

scholarly journals PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer

2020 ◽  
Author(s):  
Li Zhu ◽  
Yan-Jun Zhang ◽  
Bin Wang ◽  
Li Yang ◽  
Yi-Qiong Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Feedback Loop ◽  
Tube Formation ◽  
Migration And Invasion ◽  
Common Life ◽  
Normal Tissues ◽  
Mechanistic Investigation ◽  
Direct Target Gene ◽  
Life Threatening ◽  
Cancer Tissues

Abstract Breast cancer is one of the most common life-threatening cancers, mainly due to its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK /NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggested that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

LncRNA PCDHB17P promotes metastasis and angiogenesis of breast cancer through a miR-145-3p/MELK/NF- κ B feedback loop

2020 ◽  
Author(s):  
Li Zhu ◽  
Yan-Jun Zhang ◽  
Bin Wang ◽  
Li Yang ◽  
Yi-Qiong Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Feedback Loop ◽  
Tube Formation ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mechanistic Investigation ◽  
Cancer Tissues

Abstract Background: Breast cancer is one of the most common life-threatening cancers, mainly due to its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood.Methods: TCGA data was utilized to screen out lncRNAs dysregulated in breast cancer. The expression level of genes were analyzed and measured by RT-qPCR. The effects of PCDHB17P in breast cancer were determined in vitro and in vivo. Bioinformatics analysis was applied to predict the target between genes in breast cancer and verified via luciferase reporter assays, RNA Immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP).Results: LncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decree ased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer.Conclusions: Our research demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK /NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggested that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

scholarly journals PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer​

2020 ◽  
Author(s):  
Li Zhu ◽  
Yanjun Zhang ◽  
Bin Wang ◽  
Li Yang ◽  
Yiqiong Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Feedback Loop ◽  
Tube Formation ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mechanistic Investigation ◽  
Cancer Tissues

Abstract Background: Breast cancer is one of the most common life-threatening cancers, mainly due to its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood.Methods: TCGA data was utilized to screen out lncRNAs dysregulated in breast cancer. The expression level of genes were analyzed and measured by RT-qPCR. The effects of PCDHB17P in breast cancer were determined in vitro and in vivo. Bioinformatics analysis was applied to predict the target between genes in breast cancer and verified via luciferase reporter assays, RNA Immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP).Results: LncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decree ased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer.Conclusions: Our research demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK /NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggested that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

scholarly journals microRNA-98 inhibits the proliferation, invasion, migration and promotes apoptosis of breast cancer cells by binding to HMGA2

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Mi-Jia Wang ◽  
Hao Zhang ◽  
Jun Li ◽  
Hai-Dong Zhao
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
High Mobility ◽  
Phase Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Cancer Breast ◽  
Cancer Tissues

Breast cancer is a major contributor leading to cancer death in females worldwide. The aim of the present study was to investigate the effects of microRNA-98 (miR-98) on the processes of cell proliferation, invasion, migration and apoptosis by binding to high-mobility group AT-hook 2 (HMGA2) in breast cancer. Breast cancer tissues and adjacent normal tissues were collected from 112 patients suffering from breast cancer. The target relationship between miR-98 and HMGA2 was verified by in connection with the bioinformatics website as well as a dual-luciferase reporter assay, both of which provided evidence indicating that HMGA2 was a target gene of miR-98. Human breast cancer MDA-MB-231 cells were treated with miR-98 mimics, miR-98 inhibitors, siRNA-HMGA2 or miR-98 inhibitors + siRNA-HMGA2. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry methods were performed to determine cell proliferation, cell cycle and apoptosis, respectively, while a Transwell assay was employed to detect cell migration and invasion. Breast cancer tissues exhibited decreased miR-98 expression, while increased expression levels of HMGA2 were recorded. The mRNA and protein expressions of HMGA2, cell proliferation, cells at the S phase, cell migration, invasion, expressions of matrix metalloproteinase (MMP)2 as well as MMP9 were all reduced in response to miR-98 mimics or siRNA-HMGA2, while a contradictory trend was observed in the miR-98 inhibitors group. In conclusion, the results of the study demonstrate that miR-98 inhibits cell proliferation, migration and invasion, while acting to promote apoptosis by negatively regulating HMGA2 in breast cancer.

scholarly journals CircRNA circ_0075796 is downregulated in breast cancer and suppresses cell proliferation, migration and invasion

2021 ◽  
Author(s):  
Yao Xu ◽  
Ya-Wen Wang ◽  
Xu Chen ◽  
Can Liu ◽  
Yan-Duo Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Bioinformatics Analysis ◽  
Diagnostic Value ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Cancer Tissues ◽  
Normal Controls

Abstract Background Emerging evidence shows that circular RNAs (circRNAs) play crucial parts in tumorigenesis and progression. In this work, the expression, clinical significance, function and potential mechanism of circ_0075796 in breast cancer were explored. Methods The expression of circ_0075796 in 189 pairs of breast cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay, methyl thiazolyl tetrazolium (MTT) assay and colony formation assay were conducted for cell proliferation. Transwell assay and wound healing assay were used for cell migration and invasion. Flow cytometry analysis was adopted for cell cycle and cell apoptosis. The cellular localization of circ_0075796 was determined by fluorescence in situ hybridization (FISH). The circ_0075796/miR-452-3p/SAMD5 axis was screened out by bioinformatics analysis and verified by qRT-PCR. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m6A) modification levels of circ_0075796. QRT-PCR was used to detect the expression of RNA binding protein Quaking (QKI) in breast cancer tissues and adjacent normal tissues. Results circ_0075796 was downregulated in breast cancer tissues compared with adjacent normal tissues. In addition, circ_0075796 showed satisfactory diagnostic value to discriminate breast cancer and normal controls. Downregulated circ_0075796 expression was correlated with lymph node metastasis, HER2 expression, larger tumor size, high Ki-67 expression, advanced histological grade, aggressive molecular subtypes and advanced clinical stages. Overexpression of circ_0075796 inhibited cell proliferation, migration and invasion in vitro. FISH showed that circ_0075796 was localized in the cytoplasm and nucleus of breast cancer cells. Bioinformatics analysis and qRT-PCR revealed the potential circ_0075796/miR-452-3p/SAMD5 axis. Moreover, circ_0075796 showed lower m6A modification levels in breast cancer tissues compared to adjacent normal tissues. QKI was predicted to contain binding sites of circ_0075796 and was downregulated in breast cancer tissues compared to adjacent normal controls. Conclusions circ_0075796 was downregulated in breast cancer compared to normal controls, and showed potential diagnostic value for breast cancer. Downregulation of circ_0075796 was correlated with aggressive clinical features of breast cancer and overexpression of circ_0075796 inhibited the progression of breast cancer in vitro, indicating that circ_0075796 may be related to tumorigenesis and development of 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 Quiescin Sulfhydryl Oxidase 1 (QSOX1) Secreted by Lung Cancer Cells Promotes Cancer Metastasis

2018 ◽  
Vol 19 (10) ◽  
pp. 3213 ◽  
Author(s):  
Hye-Jin Sung ◽  
Jung-Mo Ahn ◽  
Yeon-Hee Yoon ◽  
Sang-Su Na ◽  
Young-Jin Choi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Sulfhydryl Oxidase ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
Quiescin Sulfhydryl Oxidase

As lung cancer shows the highest mortality in cancer-related death, serum biomarkers are demanded for lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS–MS proteomic analysis. Quiescin sulfhydryl oxidase (QSOX1) was selected as a biomarker candidate from the enriched proteins in the secretion of lung cancer cells. QSOX1 levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p < 0.05, Area Under curve (AUC) = 0.89) when measured by multiple reaction monitoring (MRM). Higher levels of QSOX1 were also uniquely detected in lung cancer tissues, among several other solid cancers, by immunohistochemistry. QSOX1-knock-downed Lewis lung cancer (LLC) cells were less viable from oxidative stress and reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and be involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

The glycobiological landscape of breast cancer: insights into galectins and O-GlcNAc homeostasis-related genes

2021 ◽  
Author(s):  
Rada Tazhitdinova ◽  
Alexander V Timoshenko
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Breast Cancer Subtype ◽  
The Cancer Genome Atlas ◽  
Correlation Relationship ◽  
Cancer Data ◽  
Normal Tissues ◽  
Genes Encoding ◽  
Genetic Landscape ◽  
Cancer Tissues

Abstract Purpose This study aimed to assess the functional associations between genes of the glycobiological landscape encoding galectins and O-GlcNAc cycle enzymes in the context of breast cancer biology and clinical applications. Methods An in silico analysis of the breast cancer data from The Cancer Genome Atlas was conducted comparing expression, pairwise correlations, and prognostic value for 17 genes encoding galectins, O-GlcNAc cycle enzymes, and cell stemness-related transcription factors. Results Multiple general and breast cancer subtype-specific differences in galectin/O-GlcNAc genetic landscape markers were observed and classified. Specifically, LGALS12 was found to be significantly downregulated in breast cancer tissues across all subtypes while LGALS2 and GFPT1 showed potential as prognostic markers. Remarkably, there was an overall loss of both correlation strength and correlation relationship between expression of galectin/O-GlcNAc landscape genes in the breast cancer samples versus normal tissues. Six gene pairs (GFPT1/LGALS1, GFPT1/LGALS3, GFPT1/LGALS12, GFPT1/KLF4, OGT/LGALS12, and OGT/KLF4) were found to be potential diagnostic markers for breast cancer. Conclusions These findings indicate that the glycobiological landscape of breast cancer underwent significant remodeling, which might be associated with switching galectin gene regulation within a framework of O-GlcNAc homeostasis.

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

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 303-317 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document