scholarly journals MicroRNA-101 Inhibits Growth, Proliferation and Migration and Induces Apoptosis of Breast Cancer Cells by Targeting Sex-Determining Region Y-Box 2

2017 ◽  
Vol 43 (2) ◽  
pp. 717-732 ◽  
Author(s):  
Jingjie Wang ◽  
Huijuan Zeng ◽  
Hanjun Li ◽  
Tao Chen ◽  
Lulu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Tnm Classification ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Sox2 Expression ◽  
Normal Tissues ◽  
And Migration

Background: Increasing evidence has demonstrated that microRNAs play a critical role in breast cancer (BC) progression. microRNA-101 (miR-101) has been considered a tumor suppressive miRNA in different cancer types. This study aimed to investigate miR-101 expression in BC tissues and to investigate its roles in BC progression that are mediated by Sex-determining region Y-box 2 (SOX2), a critical oncogene in various cancers. Methods: qRT-PCR and immunohistochemistry were performed to detect miR-101 and SOX2 expression in BC tissues and paired normal tissues or BC cell lines. MTT, transwell migration, wound healing, colony formation, flow cytometric and xenograft assays were performed to determine the influence of miR-101 and SOX2 on the malignant behaviors of BC cells in vitro and in vivo. Results: miR-101 was significantly downregulated in BC tissues and cell lines. miR-101 overexpression inhibited the malignant behaviors of BC cells, both in vitro and in vivo. miR-101 downregulation had the converse effect. A miR-101 binding site was identified by luciferase reporter assay in the 3’UTR of SOX2. SOX2 was upregulated in BC tissues and cell lines, and its upregulation was associated with lymph node metastasis, pathological grade and TNM classification. SOX2 knockdown mimicked the effects of miR-101 overexpression on the malignant behaviors of BC cells, while SOX2 overexpression mitigated the miR-101-induced inhibition of these effects. Conclusions: Our study revealed that miR-101 plays a critical role in suppressing tumor progression by directly targeting SOX2.

scholarly journals CircBCBM1 Promotes Breast Cancer Brain Metastasis via miR-125a/BRD4 Axis

2020 ◽  
Author(s):  
Bo Fu ◽  
Wei Liu ◽  
Peng Li ◽  
Li Pan ◽  
Ke Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Breast Cancer Patients ◽  
Breast Cancer Brain Metastasis ◽  
Tumorigenesis And Progression ◽  
And Migration

Abstract Background: Accumulating evidence indicates that circular RNAs (circRNAs) play critical roles in tumorigenesis and progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown.Methods: In this reserch, we validated the expression and characterization of circBCBM1 through RT-qPCR, Sanger sequencing, RNase R assay and fluorescence in situ hybridization (FISH). Functional experiments were performed to determine the effect of circBCBM1 on growth and metastasis of 231-BR cells both in vitro and in vivo. The regulatory mechanisms among circBCBM1, miR-125a (has-miR-125a-5p), and BRD4 (bromodomain containing 4) were investigated by RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter assay and western blot. Results: Our findings demonstrated that circBCBM1 is a stable and cytoplasmic circRNA. Functionally, silencing of circBCBM1 led to decreased proliferation and migration of 231-BR cells whereas elevated circBCBM1 expression showed reverse effects in vitro. These findings were confirmed in vivo in mouse models, as knockdown of circBCBM1 significantly decreased growth and brain metastases of 231-BR cells. Mechanistically, circBCBM1 functions as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 expression and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, the overexpression of circBCBM1 in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients.Conclusions: These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis, which sheds light on the pathogenic mechanism of circBCBM1 and provides translational evidence that circBCBM1 may serve as a novel diagnostic or prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.

scholarly journals ROS Promote Hypoxia-Induced Keratinocyte Epithelial-Mesenchymal Transition by Inducing SOX2 Expression and Subsequent Activation of Wnt/β-Catenin

2022 ◽  
Vol 2022 ◽  
pp. 1-23
Author(s):  
Yan Shi ◽  
Shang Wang ◽  
Ronghua Yang ◽  
Zhenmin Wang ◽  
Weiwei Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Mesenchymal Transition ◽  
Sox2 Expression ◽  
Subsequent Activation ◽  
And Migration

We previously showed that wound-induced hypoxia is related to keratinocyte migration. The ability of keratinocytes within wound healing to undergo epithelial to mesenchymal transition (EMT) contributes significantly to the acquisition of migratory properties. However, the effect of hypoxia on keratinocyte EMT on wound healing and the potential mechanism are poorly documented. This study first demonstrated that reactive oxygen species (ROS) appear to be an essential signalling mediator in keratinocytes with increased EMT and migration subjected to hypoxic conditions. Next, we showed that the expression of sex-determining region Y-box 2 (SOX2), a stemness-associated molecule, is ROS-dependent under hypoxia and that SOX2 inhibition in keratinocytes dramatically prevented hypoxia-induced EMT and migration. In addition, β-catenin was found to be a potential molecular target of SOX2, and the activation of Wnt/β-catenin was required for hypoxia-induced EMT and migration. Using an in vitro skin culture model and an in vivo skin wound model, our study further reinforced the critical role of ROS in inducing EMT through SOX2 expression and subsequent activation of Wnt/β-catenin, allowing for rapid reepithelialization of the wound area. Taken together, our findings reveal a previously unknown mechanism by which hypoxia promotes wound healing by promoting reepithelialization through the production of ROS, inducing keratinocyte EMT and migration via the enhancement of SOX2 and activation of Wnt/β-catenin.

scholarly journals Long Noncoding RNA HAGLROS Promotes Cell Invasion and Metastasis by Sponging miR-152 and Upregulating ROCK1 Expression in Osteosarcoma

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Kaifeng Zhou ◽  
Jun Xu ◽  
Xiaofan Yin ◽  
Jiangni Xia
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Tumor Growth And Metastasis ◽  
And Migration ◽  
Proliferation And Invasion

Background. Long noncoding RNAs (lncRNAs) played a crucial role in a number of biological processes. lncRNA HAGLROS was demonstrated to facilitate cell proliferation and migration in various cancers. However, the functions and molecular mechanisms of HAGLROS in osteosarcoma remained to be elucidated. Methods. qRT-PCR assay was used to detect the relative expression of HAGLROS in osteosarcoma tissue samples and cells. CCK-8 and Transwell assays were performed to assess the effects of HAGLROS on OS cells proliferation and invasion. Luciferase reporter assay verified the interaction between ROCK1 and miR-152. Results. In our study, we found that the expression of HAGLROS increased osteosarcoma samples and cell lines compared with normal tissues and cells. HAGLROS knockdown inhibited certain functions of U2OS and SW1353 cells in vitro. Moreover, HAGLROS depletion inhibited tumor growth and metastasis in vivo. Mechanically, we found that HAGLROS sponged miR-152 to promote ROCK1 expression in U2OS and SW1353 cells. Conclusion. In summary, our study indicated that HAGLROS could promote osteosarcoma progression by sponging miR-152 to promote ROCK1 expression. The results showed HAGLROS/miR-152/ROCK1 axis might act as a novel therapeutic strategy for osteosarcoma.

MiR-134, Mediated by IRF1, Suppresses Tumorigenesis and Progression by Targeting VEGFA and MYCN in Osteosarcoma

2020 ◽  
Vol 20 (10) ◽  
pp. 1197-1208
Author(s):  
Zhuo Ma ◽  
Kai Li ◽  
Peng Chen ◽  
Qizheng Pan ◽  
Xuyang Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Invasion And Migration ◽  
And Migration

Background: Osteosarcoma (OS) is a prevalent primary bone malignancy and its distal metastasis remains the main cause of mortality in OS patients. MicroRNAs (miRNAs) play critical roles during cancer metastasis. Objective: Thus, elucidating the role of miRNA dysregulation in OS metastasis may provide novel therapeutic targets. Methods: The previous study found a low miR-134 expression level in the OS specimens compared with paracancer tissues. Overexpression of miR-134 stable cell lines was established. Cell viability assay, cell invasion and migration assay and apoptosis assay were performed to evaluate the role of miR-134 in OS in vitro. Results: We found that miR-134 overexpression inhibits cell proliferation, migration and invasion, and induces cell apoptosis in both MG63 and Saos-2 cell lines. Mechanistically, miR-134 targets the 3'-UTR of VEGFA and MYCN mRNA to silence its translation, which was confirmed by luciferase-reporter assay. The real-time PCR analysis illustrated that miR-134 overexpression decreases VEGFA and MYCN mRNA levels. Additionally, the overexpression of VEGFA or MYCN can partly attenuate the effects of miR-134 on OS cell migration and viability. Furthermore, the overexpression of miR-134 dramatically inhibits tumor growth in the human OS cell line xenograft mouse model in vivo. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-134 is regulated by Interferon Regulatory Factor (IRF1), which binds to its promoter and activates miR-134 expression. Conclusion: Our study demonstrates that IRF1 is a key player in the transcriptional control of miR-134, and it inhibits cell proliferation, invasion and migration in vitro and in vivo via targeting VEGFA and MYCN.

scholarly journals MiR-137 Suppresses Triple-Negative Breast Cancer Stemness and Tumorigenesis by Perturbing BCL11A-DNMT1 Interaction

2018 ◽  
Vol 47 (5) ◽  
pp. 2147-2158 ◽  
Author(s):  
Feiyu Chen ◽  
Na Luo ◽  
Yu Hu ◽  
Xin Li ◽  
Kejing  Zhang
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Tumor Development ◽  
Cancer Stemness ◽  
Normal Tissues ◽  
Tumor Tissues

Background/Aims: Triple negative breast cancer (TNBC) is resistant to conventional chemotherapy due to high proportions of cancer stem cells (CSCs). The aim of this study is to unravel the miR-137-mediated regulatory mechanism of B-cell lymphoma/leukemia 11A (BCL11A) in TNBC. Methods: A corhort of 34 TNBC tumor tissues and paired adjacent normal tissues, as well as 25 non-TNBC tumor tissues and paired adjacent normal tissues were collected post-operatively from patients with breast cancer. Q-PCR was performed to determine the mRNA levels of miR-137 and BCL11A in breast tissues and cell lines. Bioinformatics analysis and dual luciferase reporter assay were used to verify the direct interaction between miR-137 and BCL11A. After up-/down-regulation of BCL11A, miR-137, or DNMT1 via lentiviral transduction in TNBC cell lines SUM149 and MDA-MB-231 cells, Q-PCR and Western blot assays were used to detect the expression levels of BCL11A, DNA methyltransferases 1 (DNMT1), and Islet-1 (ISL1). Mammosphere assay was conducted to assess tumorosphere formation ability of cells, coupled with flow cytometry to determine the percentage of breast cancer stem cells. Co-immunoprecipitation assay was used to determine the interaction between BCL11A and DNMT1. Xenograft tumorigenesis assay was performed to monitor tumor formation in vivo. Results: BCL11A was highly expressed in TNBC, whereas miR-137 was significantly lower in both TNBC tissues and cell lines. miR-137 suppressed BCL11A expression at both mRNA and protein levels by directly targeting its 3’UTR. In both SUM149 and MDA-MB-231 cells, overexpression of miR-137 or knockdown of BCL11A reduced the number of tumoroshperes and the percentage of cancer stem cells in vitro, and inhibited tumor development in vivo. Furthermore, BCL11A interacted with DNMT1 in TNBC cells. Silencing of either BCL11A or DNMT1 impaired cancer stemness and tumorigenesis of TNBC via suppressing ISL1 expression both in vitro, and in vivo. Conclusions: By perturbing BCL11A-DNMT1 interaction, miR-137 impairs cancer stemness and suppresses tumor development in TNBC.

scholarly journals MiR-664b-3p Inhibited Triple-Negative Breast Cancer Cell Growth Via Targeting BRIP1

2021 ◽  
Author(s):  
Qiu Jin ◽  
Bo Lin ◽  
Wenhui Zhao ◽  
Runyuan Ji
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Luciferase Reporter ◽  
Breast Cancer Cell Growth ◽  
Cell Functions

Abstract BackgroundMany studies indicate that microRNAs (miRNAs) play a crucial role in modulating the development and progression of triple-negative breast cancer (TNBC). However, miR-664b-3p affections on the TNBC functions and mechanisms are still unknown. The purpose of our study was to clarify the effects of miR-664b-3p in cellular TNBC development and progression.MethodsIn our study, the expressions of miR-664b-3p in cell lines and tissueswere tested by real-time PCR (RT-PCR), immunofluorescence, H&E and immunohistochemistry staining. CCK-8 assay, colony formation, EdU, flow cytometry apoptosis, wound scratch, Transwell assays were applied to explore the cell functions. The targeted relationship between miR-664b-3p and its target BRIP1 was determined by dual-luciferase reporter assay and rescue experiments. ResultsWe observed that miR-664b-3p was significantly decreased in TNBC cell lines. Overexpression of miR-664b-3p could observably inhibit cell proliferation, migration, invasion and induced apoptosis in vitro. Meanwhile, miR-664-3p suppressed TNBC tumor growth in vivo. Furthermore, luciferase reporter assays identified the interaction between 3’UTR of BRIP1 and miR-664b-3p. Moreover, we investigated the mechanisms underlying the effect of miR-664b-3p on cell functions, and the result showed that miR-664b-3p inhibited cell proliferation, invasion and accelerated apoptosis by targeting BRIP1.ConclusionFrom the above, our findings indicated that miR-664b-3p played a significant role in TNBC progression by targeting BRIP1, providing new therapeutic targets for diagnostic in TNBC.

scholarly journals SIPL1, Regulated by MAZ, Promotes Tumor Progression and Predicts Poor Survival in Human Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Juanjuan He ◽  
Jing Wang ◽  
Teng Li ◽  
Kunlun Chen ◽  
Songchao Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Zinc Finger Protein ◽  
Disease Free Survival ◽  
Luciferase Reporter ◽  
Breast Epithelial Cell

BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer owing to a lack of effective targeted therapy and acquired chemoresistance. Here, we explored the function and mechanism of shank-interacting protein-like 1 (SIPL1) in TNBC progression.MethodsSIPL1 expression was examined in human TNBC tissues and cell lines by quantitative reverse transcription PCR, western blot, and immunohistochemistry. SIPL1 overexpression and silenced cell lines were established in BT-549 and MDA-MB-231 cells. The biological functions of SIPL1 in TNBC were studied in vitro using the CCK-8 assay, CellTiter-Glo Luminescent Cell Viability assay, caspase-3/8/9 assay, wound healing assay, and transwell assay and in vivo using a nude mouse model. The potential mechanisms underlying the effects of SIPL1 on TNBC progression were explored using bioinformatics analysis, luciferase reporter assays, and chromatin immunoprecipitation followed by qPCR.ResultsSIPL1 expression was higher in human TNBC tissues and cell lines than in adjacent normal tissues and a breast epithelial cell line (MCF10A). High expression of SIPL1 was positively correlated with poor overall and disease-free survival in patients with TNBC. SIPL1 overexpression elevated and SIPL1 silencing repressed the malignant phenotypes of TNBC cells in vitro. SIPL1 overexpression promoted xenograft tumor growth in vivo. Myc-associated zinc-finger protein (MAZ) transcriptionally activated SIPL1. Finally, we found that SIPL1 promoted TNBC malignant phenotypes via activation of the AKT/NF-κB signaling pathways.ConclusionsThese results indicate that the MAZ/SIPL1/AKT/NF-κB axis plays a crucial role in promoting the malignant phenotypes of TNBC cells.

scholarly journals Linc-SCRG1 accelerates progression of hepatocellular carcinoma as a ceRNA of miR26a to derepress SKP2

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jun-Jie Hu ◽  
Cui Zhou ◽  
Xin Luo ◽  
Sheng-Zheng Luo ◽  
Zheng-Hong Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Colony Formation ◽  
S Phase ◽  
Luciferase Reporter ◽  
And Migration ◽  
Hcc Cells ◽  
Proliferation And Migration

Abstract Background Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) have regulatory functions in hepatocellular carcinoma (HCC). The link between lincSCRG1 and HCC remains unclear. Methods To explore the lincSCRG1 regulation axis, bioinformatics, RIP and luciferase reporter assay were performed. The expressions of lincSCRG1-miR26a-SKP2 were detected in HCC tissues and cell lines through qPCR and western blot. The functions of HCC cells were investigated through in vitro assays (MTT, colony formation, transwell and flow cytometry) and the inner effect of lincSCRG1-miR26a in vivo was evaluated by xenografts and liver metatstatic nude mice models. Results LincSCRG1 was found to be strongly elevated in human HCC tissues and cell lines. MiR26a and S phase kinase-related protein 2 (SKP2) were predicted as the target miRNA for lincSCRG1 and the target gene for miR26a with direct binding sites, respectively. LincSCRG1 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR26a and derepression of SKP2 in HCC cells. Both overexpression of lincSCRG1 (ov-lincSCRG1) and inhibition of miR26a (in-miR26a) obviously stimulated cellular viability, colony formation, migration and proliferation of S phase cells and also significantly increased the protein levels of cyclinD1, CDK4, MMP2/3/9, Vimentin, and N-cadherin or inhibited the protein level of E-cadherin of HCC cells, while knockdown of lincSCRG1 (sh-lincSCRG1) and upregulation of miR26a (mi-miR26a) had the opposite effects on HCC cells. Cotransfection of in-miR26a or overexpression of SKP2 (ov-SKP2) with sh-lincSCRG1 could rescue the anticancer functions of sh-lincSCRG1, including suppressing proliferation and migration of HCC cells. Additionally, sh-lincSCRG1 could effectively inhibit the growth of subcutaneous xenograft tumours and lung metastasis, while the anticancer effect of sh-lincSCRG1 could be reversed by cotransfection of in-miR26a. Conclusions LincSCRG1 acts as a ceRNA of miR26a to restrict its ability to derepress SKP2, thereby inducing the proliferation and migration of HCC cells in vitro and in vivo. Depletion of lincSCRG1 could be used as a potential therapeutic approach in HCC.

scholarly journals Chemokine CXCL16 Expression Suppresses Migration and Invasiveness and Induces Apoptosis in Breast Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yeying Fang ◽  
Fraser C. Henderson ◽  
Qiong Yi ◽  
Qianqian Lei ◽  
Yan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
And Migration ◽  
Cxcl16 Expression

Background.Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cellsin vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells.Methods.Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels.In vitroandin vivostudies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells.Results.We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with thein vitrodata, CXCL16 overexpression inhibited tumorigenesisin vivo.Conclusions.Cellular CXCL16 suppresses invasion and metastasis of breast cancer cellsin vitroand inhibits tumorigenesisin vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.

scholarly journals miR-22-3p/PGC1β Suppresses Breast Cancer Cell Tumorigenesis via PPARγ

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xuehui Wang ◽  
Zhilu Yao ◽  
Lin Fang
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Therapeutic Target ◽  
Opposite Effect ◽  
Potential Biomarker ◽  
And Migration ◽  
Proliferation And Migration

In this study, we found that miR-22-3p expression was decreased in breast cancer (BC) cell lines and tissues. Overexpression of miR-22-3p inhibited the proliferation and migration of BC cells in vitro and in vivo, while depletion of miR-22-3p exhibited the opposite effect. Importantly, miR-22-3p could directly target PGC1β and finally regulate the PPARγ pathway in BC. In conclusion, miR-22-3p/PGC1β suppresses BC cell tumorigenesis via PPARγ, which may become a potential biomarker and therapeutic target.

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