Silence of lncRNA MIAT-mediated inhibition of DLG3 promoter methylation suppresses breast cancer progression via the Hippo signaling pathway

2020 ◽  
Vol 73 ◽  
pp. 109697 ◽  
Author(s):  
Dezhi Li ◽  
Xingsheng Hu ◽  
Sijia Yu ◽  
Shishan Deng ◽  
Min Yan ◽  
...  
Author(s):  
Kun Qiao ◽  
Shipeng Ning ◽  
Lin Wan ◽  
Hao Wu ◽  
Qin Wang ◽  
...  

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.


2020 ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Qifeng Luo ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
...  

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


Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  

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.


2019 ◽  
Vol 9 ◽  
Author(s):  
Wei Wang ◽  
Xiaolong Wang ◽  
Chen Li ◽  
Tong Chen ◽  
Ning Zhang ◽  
...  

2012 ◽  
Vol 48 ◽  
pp. S108
Author(s):  
A.S. Ribeiro ◽  
A. Vieira ◽  
B. Sousa ◽  
A. Albergaria ◽  
R. Seruca ◽  
...  

2021 ◽  
Author(s):  
Maonan Wang ◽  
Manli Dai ◽  
Dan Wang ◽  
Ting Tang ◽  
Fang Xiong ◽  
...  

Abstract BackgroundLong noncoding RNAs (lncRNAs) play an important role in the regulation of gene expression and are involved in several pathological responses. However, many important lncRNAs in breast cancer have not been identified and their expression levels and functions in breast cancer remain unknown.MethodsWe used the microarray data to identify differentially expressed lncRNAs between breast cancer and adjacent breast epithelial tissues. In vitro and in vivo assays were used to explore the biological effects of the differentially expressed lncRNA Apoptosis-Associated Transcript in Bladder Cancer (AATBC) in breast cancer cells. The mass spectrometry and RNA pulldown were used to screen AATBC interacting proteins. Using the Kaplan-Meier method, survival analysis was performed.ResultsThe expression of AATBC was significantly high in breast cancer samples, and this high AATBC level was tightly correlated with poor prognosis in breast cancer patients. In vitro and in vivo experiments indicated that AATBC promoted breast cancer cells migration and invasion. AATBC specifically interacted with Y-box binding protein 1 (YBX1), which activated the YAP1/Hippo signaling pathway by binding to macrophage stimulating 1 (MST1) and promoting the nuclear translocation of Yes associated protein 1 (YAP1), allowing its function as a nuclear transcriptional regulator. ConclusionsAATBC is highly expressed in breast cancer and contributes to patients’ progression, indicating that it could serve as a novel prognostic marker for the disease. Mechanistically, AATBC affects migration and invasion of breast cancer cells through an AATBC-YBX1-MST1 axis, resulting in activating the YAP1/Hippo signaling pathway. This is also an important supplement to the composition of the YAP1/Hippo signaling pathway. The model of “AATBC-YAP1” may bring a new dawn to the treatment of breast cancer.


2018 ◽  
Vol 57 (12) ◽  
pp. 1792-1802 ◽  
Author(s):  
Yunxiao Liu ◽  
Yanyan Dong ◽  
Liping Zhao ◽  
Lihong Su ◽  
Kexin Diao ◽  
...  

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