Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis

Wu, Xiaoqing; Gardashova, Gulhumay; Lan, Lan; Han, Shuang; Zhong, Cuncong; Marquez, Rebecca T.; Wei, Lanjing; Wood, Spencer D.; Roy, Sudeshna; Gowthaman, Ragul; Karanicolas, John; Gao, Fei; Dixon, Dan A.; Welch, Danny R.; Li, Ling; Ji, Min; Aubé, Jeffrey; Xu, Liang

doi:10.1038/s42003-020-0933-1

Cited by 73 publications

(72 citation statements)

References 60 publications

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“…Treatment with KH-3 in vivo inhibited breast tumor growth comparing to that of vehicle control. Furthermore, the inhibitory capability of KH-3 on cancer cells was attenuated by HuR stable knockdown with the lentiviral shRNA, indicating the target selectivity of KH-3 [27]. Importantly, inhibition of HuR with KH-3 yielded a significant reduced in the progression of pathological cardiac hypertrophy in a transverse aortic constriction model, as evidenced by a reduction in hypertrophy, dilation and fibrosis, and preserved cardiac function [28].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we have discovered a series of small molecule HuR inhibitors at nM to sub-μM K i values, which dose-dependently inhibit the action of HuR by specifically disrupting HuR-ARE interaction [25,26]. The lead compound KH-3 exhibits superior potency in disrupting HuR-ARE interaction [27]. It has been shown that KH3 selectively inhibited the viability of cancer cells that had high levels of HuR but had no effect on normal cell line in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of RNA-binding protein HuR reduces glomerulosclerosis in experimental nephritis

et al. 2020

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Recent identification of an RNA-binding protein (HuR) that regulates mRNA turnover and translation of numerous transcripts via binding to an ARE in their 3′-UTR involved in inflammation and is abnormally elevated in varied kidney diseases offers a novel target for the treatment of renal inflammation and subsequent fibrosis. Thus, we hypothesized that treatment with a selective inhibition of HuR function with a small molecule, KH-3, would down-regulate HuR-targeted proinflammatory transcripts thereby improving glomerulosclerosis in experimental nephritis, where glomerular cellular HuR is elevated. Three experimental groups included normal and diseased rats treated with or without KH-3. Disease was induced by the monoclonal anti-Thy 1.1 antibody. KH-3 was given via daily intraperitoneal injection from day 1 after disease induction to day 5 at the dose of 50 mg/kg BW/day. At day 6, diseased animals treated with KH-3 showed significant reduction in glomerular HuR levels, proteinuria, podocyte injury determined by ameliorated podocyte loss and podocin expression, glomerular staining for periodic acid-Schiff positive extracellular matrix proteins, fibronectin and collagen IV and mRNA and protein levels of profibrotic markers, compared with untreated disease rats. KH-3 treatment also reduced disease-induced increases in renal TGFβ1 and PAI-1 transcripts. Additionally, a marked increase in renal NF-κB-p65, Nox4, and glomerular macrophage cell infiltration observed in disease control group was largely reversed by KH-3 treatment. These results strongly support our hypothesis that down-regulation of HuR function with KH-3 has therapeutic potential for reversing glomerulosclerosis by reducing abundance of pro-inflammatory transcripts and related inflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of RNA-binding protein HuR reduces glomerulosclerosis in experimental nephritis

et al. 2020

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“…[26][27][28][29][30][31] Increasing numbers of studies have examined the role of FOXQ1 in tumor progression and it has been suggested that suppressing FOXQ1 expression may decrease invasion and migration in TNBC cell lines. 32,33 FOXQ1 has also been suggested as potentially being a driving force in the heterogeneity of BC. 6 Thus, additional knowledge of the role of FOXQ1 in BC could have the potential to improve the diagnosis and treatment of BC tumors.…”

Section: Introductionmentioning

confidence: 99%

FOXQ1 is Differentially Expressed Across Breast Cancer Subtypes with Low Expression Associated with Poor Overall Survival

Elian¹,

Are²,

Ghosh³

et al. 2021

BCTT

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Purpose: Forkhead box Q1 (FOXQ1) has been shown to contribute to the development and progression of cancers, including ovarian and breast cancer (BC). However, research exploring FOXQ1 expression, copy number variation (CNV), and prognostic value across different BC subtypes is limited. Our purpose was to evaluate FOXQ1 mRNA expression, CNV, and prognostic value across BC subtypes. Materials and Methods: We determined FOXQ1 expression and CNV in BC patient tumors using RT-qPCR and qPCR, respectively. We also analyzed FOXQ1 expression and CNV in BC cell lines in the CCLE database using K-means clustering. The prognostic value of FOXQ1 expression in the TCGA-BRCA database was assessed using univariate and multivariate Cox's regression analysis as well as using the online tools OncoLnc, GEPIA, and UALCAN. Results: Our analyses reveal that FOXQ1 mRNA is differentially expressed between different subtypes of BC and is significantly decreased in luminal BC and HER2 patients when compared to normal breast tissue samples. Furthermore, analysis of BC cell lines showed that FOXQ1 mRNA expression was independent of CNV. Moreover, patients with low FOXQ1 mRNA expression had significantly poorer overall survival compared to those with high FOXQ1 mRNA expression. Finally, low FOXQ1 expression had a critical impact on the prognostic values of BC patients and was an independent predictor of overall survival when it was adjusted for BC subtypes and to two other FOX genes, FOXF2 and FOXM1. Conclusion: Our study reveals for the first time that FOXQ1 is differentially expressed across BC subtypes and that low expression of FOXQ1 is indicative of poor prognosis in patients with BC.

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“…Notably, through interaction with a variety of RNA binding proteins (RBPs), lncRNAs are known to participate in the regulation of RNA splicing and stability [ 64 ]. For instance, the RNA binding protein ELAVL1 (embryonic lethal abnormal vision-like protein 1), also known as HuR (Hu antigen R), is crucial for the nuclear import and stabilization of numerous RNA transcripts [ 65 ]. In OSCC, the oncogenic lncRNA SNHG3 (small nucleolar RNA host gene 3) was reported to be localized in the cytoplasm and capable of recruiting ELAVL1, and thereby stabilizing NFYC (transcription factor Y subunit gamma) mRNA to upregulate the expression of NFYC, which in turn promotes cell proliferation and migration [ 66 ] ( Figure 1 e).…”

Section: Mechanism Of Oral Cancer-associated Lncrnas In Tumorigenesismentioning

confidence: 99%

Long Non-Coding RNAs as Functional Codes for Oral Cancer: Translational Potential, Progress and Promises

Lei

Kung

Shih

2021

IJMS

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Oral cancer is one of the leading malignant tumors worldwide. Despite the advent of multidisciplinary approaches, the overall prognosis of patients with oral cancer is poor, mainly due to late diagnosis. There is an urgent need to develop valid biomarkers for early detection and effective therapies. Long non-coding RNAs (lncRNAs) are recognized as key elements of gene regulation, with pivotal roles in various physiological and pathological processes, including cancer. Over the past few years, an exponentially growing number of lncRNAs have been identified and linked to tumorigenesis and prognosis outcomes in oral cancer, illustrating their emerging roles in oral cancer progression and the associated signaling pathways. Herein, we aim to summarize the most recent advances made concerning oral cancer-associated lncRNA, and their expression, involvement, and potential clinical impact, reported to date, with a specific focus on the lncRNA-mediated molecular regulation in oncogenic signaling cascades and oral malignant progression, while exploring their potential, and challenges, for clinical applications as biomarkers or therapeutic targets for oral cancer.

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Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis

Cited by 73 publications

References 60 publications

Inhibition of RNA-binding protein HuR reduces glomerulosclerosis in experimental nephritis

Inhibition of RNA-binding protein HuR reduces glomerulosclerosis in experimental nephritis

FOXQ1 is Differentially Expressed Across Breast Cancer Subtypes with Low Expression Associated with Poor Overall Survival

Long Non-Coding RNAs as Functional Codes for Oral Cancer: Translational Potential, Progress and Promises

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