scholarly journals Crosstalk Among YAP, LncRNA, and Tumor-Associated Macrophages in Tumorigenesis Development

2022 ◽  
Vol 11 ◽  
Author(s):  
Jing Xu ◽  
Xin-Yuan Liu ◽  
Qi Zhang ◽  
Hua Liu ◽  
Peng Zhang ◽  
...  

Long non-coding RNAs (ncRNAs), which do not encode proteins, regulate cell proliferation, tumor angiogenesis, and metastasis and are closely associated with the development, progression, and metastasis of many cancers. Tumor-associated macrophages (TAMs) in the tumor microenvironment play an important role in cancer progression. The Hippo signaling pathway regulates cell proliferation and apoptosis, maintains tissue and organ size, and homeostasis of the internal environment of organisms. Abnormal expression of Yes-associated protein (YAP), the Hippo signaling pathway key component, is widely observed in various malignancies. Further, TAM, lncRNA, and YAP are currently valuable targets for cancer immunotherapy. In this review, we have logically summarized recent studies, clarified the close association between the three factors and tumorigenesis, and analyzed the outlook of tumor immunotherapy.

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 ◽  
Vol Volume 13 ◽  
pp. 1737-1749 ◽  
Author(s):  
Zhiqiang Wu ◽  
Chunmeng Wang ◽  
Yong Chen ◽  
Zhengwang Sun ◽  
Wangjun Yan

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


2020 ◽  
Author(s):  
Li na Wang ◽  
Dong run Tang ◽  
Tong Wu ◽  
Feng yuan Sun

Abstract Background: Malignant melanoma is the deadliest of skin cancer. The present study aimed to elucidate potential key candidate genes in melanoma and its molecular mechanism. Methods: Three gene expression profile data sets (GSE46517, GSE52882 and GSE54493) were downloaded from the GEO database, which included data from melanoma tissue samples and cell lines. DEGs were subsequently investigated by GO analysis via using DAVID website. PPI network was constructed using the STRING database and visualized by Cytoscape software and MCODE were utilized to PPI network to pick out meaningful DEGs. Cell proliferation, apoptosis, migration and invasion were measured using CCK-8, colony formation, flow cytometry, transwell and wound healing assays. RT-PCR, western blotting and immunohistochemistry assays were used to detect mRNA and protein expressions. TCGAportal and GEPIA databases were used to perform the bioinformatics analysis of LTBP4 in melanoma. Results: LTBP4 both is the DEG and a key gene from the most significant module of the PPI network. LTBP4 expression was down-regulation in melanoma tissues and cells relative to controls, which showed positive correlation with invasion, TNM stage, distal metastasis and lymph node metastasis, and predicted the poor prognosis for patients with melanoma. Cox analysis identified LTBP4 low-expression as an independent prognostic variable for overall survival (OS) in patients with melanoma. The results revealed that LTBP4 inhibition reduced cell apoptosis, promoted cell proliferation and metastasis. These changes were correlated caspase-3, ki67 and E-cadherin expressions by western blotting assay. Further in vivo tumor formation study in nude mice indicated that LTBP4 inhibition promoted the progress of tumor formation. LTBP4 gene knockout reduced the phosphorylation level of YAP, MST1 and MOB1 and promoted the nuclear translocation of YAP to inhibit the activation of Hippo signaling pathway. The functions of LTBP4 overexpression (OE) inhibiting the expressions of CTGF, Cyr61 and Birc5, promoting the apoptosis, and inhibiting the metastasis and proliferation of melanoma cells were reversed by YAP/or MST1 OE.Conclusions: LTBP4 OE suppressed the proliferation and metastasis in melanoma via inhibiting the nuclear translocation of YAP to activating Hippo signaling pathway, thereby inhibiting the development and progression of melanoma.


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