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

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

scholarly journals LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Kun Qiao ◽  
Shipeng Ning ◽  
Lin Wan ◽  
Hao Wu ◽  
Qin Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Hippo Signaling ◽  
Cancer Cell Proliferation ◽  
Chip Assay ◽  
Breast Cancer Cell Proliferation ◽  
Hippo Signaling Pathway ◽  
Cancer Tissues

Abstract Background An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we explored the function and detailed mechanisms of long intergenic nonprotein coding RNA 673 (LINC00673) in breast cancer progression. Methods Quantitative real-time PCR (qRT-PCR) was used to examine the expression of LINC00673 in breast cancer tissues and in adjacent normal tissues. Gain-of-function and loss-of function experiments were conducted to investigate the biological functions of LINC00673 in vitro and in vivo. We also explored the potential role of LINC00673 as a therapeutic target using antisense oligonucleotide (ASO) in vivo. RNA sequencing (RNA-seq), dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assay, and rescue experiments were performed to uncover the detailed mechanism of LINC00673 in promoting breast cancer progression. Results In the present study, LINC00673 displayed a trend of remarkably increased expression in breast cancer tissues and was associated with poor prognosis in breast cancer patients. Importantly, LINC00673 depletion inhibited breast cancer cell proliferation by inhibiting the cell cycle and increasing apoptosis. Furthermore, ASO therapy targeting LINC00673 substantially suppressed breast cancer cell proliferation in vivo. Mechanistically, LINC00673 was found to act as a ceRNA by sponging miR-515-5p to regulate MARK4 expression, thus inhibiting the Hippo signaling pathway. Finally, ChIP assay showed that the transcription factor Yin Yang 1 (YY1) could bind to the LINC00673 promoter and increase its transcription in cis. Conclusions YY1-activated LINC00673 may exert an oncogenic function by acting as a sponge for miR-515-5p to upregulate the MARK4 and then inhibit Hippo signaling pathway, and may serve as a potential therapeutic target.

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 miR-425 suppresses EMT and inhibits the development of TNBC (triple-negative breast cancer) by targeting TGF-β 1/SMAD 3 signaling pathway

2018 ◽  
Author(s):  
Yingping Liu ◽  
Hongfei Qiao ◽  
Jinglong Chen
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Mesenchymal Cell ◽  
Cell Proliferation And Migration ◽  
Tnbc Cell ◽  
Tumor Tissues ◽  
And Migration ◽  
Tgf Β1 ◽  
Proliferation And Migration

AbstractBackgroundEMT has the crucial effect on the progression and metastasis of tumor. This work will elucidate the role of miR-425 in EMT and development of TNBC.MethodsThe differential miRNA expression among non-tumor, para-tumor (adjacent tissue of tumor) and tumor tissues was analyzed. The luciferase activities of TGF-β1 3’ UTR treated with miR-425 were determined. Then human breast cancer cell lines were dealt with mimics or inhibitors of miR-425, and then the cell proliferation and migration, invasion ability were assessed. The expression of TGF-β1 and markers of epithelial cell and mesenchymal cell were analyzed. The influences of miR-425 on development of TNBC through inducing EMT by targeting TGF-β 1 and TGF-β1/SMAD3 signaling pathway in TNBC cell lines were investigated. Furthermore, Xenograft mice were used to explore the potential roles of miR-425 on EMT and development of TNBC in vivo.ResultsCompared with non-tumor tissues, 9 miRNAs were upregulated and 3 miRNAs were down-regulated in tumor tissues. The relative expression of miR-425 in tumor tissues was obviously much lower than that in para-tumor and non-tumor tissues. MiR-425 suppressed TGF-β1 expression, additionally inhibited expression of mesenchymal cell markers, while exerted effects on cell proliferation and migration of TNBC cell lines. Moreover, the agomir of miR-425 could protect against development process in murine TNBC xenogarft model.ConclusionsOur results demonstrated that miR-425 targets to TGF-β1, and was a crucial suppressor on EMT and development of TNBC through inhibiting TGF-β1/SMAD3 signaling pathway. It suggested that aim at TGF-β1/SMAD3 signaling pathway by enhancing relative miR-425 expression, was a feasible therapy strategy for TNBC.

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 Linc00887 suppresses tumorigenesis of cervical cancer through regulating the miR-454-3p/FRMD6-Hippo axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pei Li ◽  
Jinsheng Wang ◽  
Lingran Zhi ◽  
Fengmei Cai
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Hippo Signaling ◽  
Luciferase Reporter Gene ◽  
Hippo Signaling Pathway ◽  
Cancer Tissues ◽  
Proliferation And Invasion

Abstract Background Emerging evidence suggested that long intergenic noncoding RNA (lincRNA) 00887 (NR_024480) reduced the invasion and metastasis of non-small cell lung cancer by sponging miRNAs degradation. However, the role and regulatory mechanism of linc00887 in the progression of cervical cancer remain largely unknown. Methods In vivo or vitro, RT-qPCR assay was used to detect the expression of linc00887 in human normal (N = 30), cervical cancer tissues (N = 30), human normal cervical epithelial cells (Ect1/E6E7) and cervical cancer cell lines (HeLa, C33A). Then, CCK-8 and Transwell assays were used to examine cell proliferation and invasion when linc00887 was overexpressed or knocked down. In addition, bioinformatics, luciferase reporter gene and pull-down assays were used to predict and validate the relationship between linc00887 and miR-454-3p. Moreover, we detected the expression of miR-454-3p in Ect1/E6E7, HeLa and C33A cells when linc00887 was overexpressed or knocked down. Cell proliferation and invasion were also measured when pcDNA-linc00887 and miR-454-3p were transfected alone or together. Next, miR-454-3p target gene was predicted and validated by bioinformatics and luciferase reporter gene assays. Gain- and loss-of-function experiments were performed in HeLa cells to evaluate the effect of miR-454-3p or linc00887 on the expression of FERM domain containing protein 6 (FRMD6) protein and several key proteins in the FRMD6-Hippo signaling pathway. Results Linc00887 was downregulated in cervical cancer tissues or human cervical cancer cell lines (Hela, C33A) compared with normal tissues or cell lines. Overexpression of linc00887 inhibited proliferation and invasion HeLa and C33A cells, while linc00887 knockdown had the opposite effect. Linc00887 bound with miR-454-3p, and overexpression of miR-454-3p rescued linc00887-induced inhibition proliferation and invasion of HeLa cells. MiR-454-3p targeted and suppressed the expression of FRMD6, and linc00887 suppressed tumorigenesis of cervical cancer through activating the FRMD6-Hippo signaling pathway. Conclusions Linc00887, sponging miR-454-3p, inhibited the progression of cervical cancer by activating the FRMD6-Hippo signaling pathway.

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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