scholarly journals miR‑149‑5p promotes chemotherapeutic resistance in ovarian cancer via the inactivation of the Hippo signaling pathway

Author(s):  
Manman Xu ◽  
Juan Xiao ◽  
Ming Chen ◽  
Linjing Yuan ◽  
Jundong Li ◽  
...  
2020 ◽  
Author(s):  
Yan Li ◽  
Qi Wang ◽  
Ning Ning ◽  
Fanglan Tang ◽  
Yan Wang

Abstract Background Ovarian cancer (OC) is the major cause of death among women due to the lack of early screening methods and complex pathological progression. Increasing evidence indicated that microRNAs were considered as gene expression regulators in tumors by interacting with mRNAs. Although researches regarding with OC and microRNAs are extensive, the vital role of MIR502 in OC still remains unclear.Methods We integrated two microRNA expression arrays from GEO to identify differentially expressed genes. Kaplan–Meier method was used to screen miRNAs that had influence on survival outcome. Upstream regulator of MIR502 was predicted by JASPAR and verified by ChIP-seq data. The LinkedOmics database was used to study correlated genes with MIR502. Gene Set Enrichment Analysis (GSEA) was conducted to reveal the functional annotation of GO and KEGG pathway enrichment analysis by using the open access WebGestalt tool. We constructed PPI network by using the STRING to further explore core protein.Results We found that expression level of MIR502 was significantly down regulated in OC, which was related to poor overall survival outcome. NRF1 as the upstream regulator of MIR502 was predicted by JASPAR and verified by ChIP-seq data. In addition, anti-apoptosis and pro-proliferation genes attending in Hippo signaling pathway, including CCND1, MYC, FGF1 and GLI2 were negatively regulated by MIR502 in the analysis of GO and KEGG pathway enrichment results. PPI network further demonstrated that CCND1 and MYCN were at core position in the development of ovarian cancer.Conclusions MIR502, which was regulated by NRF1, acted as a tumor suppressor gene to accelerate apoptosis and suppress proliferation by targeting Hippo signaling pathway in ovarian cancer.


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.


2021 ◽  
Vol 22 (2) ◽  
pp. 931
Author(s):  
Jihyun Lee ◽  
Yujin Jung ◽  
Seo won Jeong ◽  
Ga Hee Jeong ◽  
Gue Tae Moon ◽  
...  

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.


2015 ◽  
Vol 57 (4) ◽  
pp. 341-351 ◽  
Author(s):  
Shinichi Hayashi ◽  
Hitoshi Yokoyama ◽  
Koji Tamura

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