RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

Zhao, Jing; Liu, Xi‐sheng; Zhu, Fangming; Xie, Feng; Jiang, Chuanwen; Zhang, Zi‐ye; Gao, Yunzhen; Wang, Yongchuan; Li, Bin; Xia, Shujie; Han, Bangmin

doi:10.1111/cas.14280

Cited by 21 publications

(24 citation statements)

References 54 publications

(66 reference statements)

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“…The plasmids of human wildtype NRP1 3′-UTR and miR185-3p-binding site mutated NRP1 3′-UTR were constructed as described previously 56 . To determine the miR-185-3p/ NRP1 mRNA interaction, HEK 293T cells were seeded in 24-well plates, and reporter gene constructs were co-transfected into cells with miR-185-3p mimic or inhibitor for 48 h. An expression vector encoding Renilla luciferase at a 1:50 ratio was included during the transfection.…”

Section: Methodsmentioning

confidence: 99%

“…To determine the miR-185-3p/ NRP1 mRNA interaction, HEK 293T cells were seeded in 24-well plates, and reporter gene constructs were co-transfected into cells with miR-185-3p mimic or inhibitor for 48 h. An expression vector encoding Renilla luciferase at a 1:50 ratio was included during the transfection. And the detailed information was same as described previously 56 .…”

Section: Methodsmentioning

confidence: 99%

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Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis

et al. 2021

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Increasing evidence suggests that global downregulation of miRNA expression is a hallmark of human cancer, potentially due to defects in the miRNA processing machinery. In this study, we found that the protein expression of Argonaute 2 (AGO2), a key regulator of miRNA processing, was downregulated in colorectal cancer (CRC) tissues, which was also consistent with the findings of the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Furthermore, the correlation between the levels of AGO2 and epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) indicated that reduced levels of AGO2 promoted EMT in CRC. Low expression of AGO2 was an indicator of a poor prognosis among CRC patients. Knockdown of AGO2 in CRC cells promoted migration, invasion and metastasis formation in vitro and in vivo but had no influence on proliferation. To provide detailed insight into the regulatory roles of AGO2, we performed integrated transcriptomic, quantitative proteomic and microRNA sequencing (miRNA-seq) analyses of AGO2 knockdown cells and the corresponding wild-type cells and identified neuropilin 1 (NRP1) as a new substrate of AGO2 via miR-185-3p. Our data provided evidence that knockdown of AGO2 resulted in a reduction of miR-185-3p expression, leading to the upregulation of the expression of NRP1, which is a direct target of miR-185-3p, and elevated CRC cell metastatic capacity. Inhibition of NRP1 or treatment with a miR-185-3p mimic successfully rescued the phenotypes of impaired AGO2, which suggested that therapeutically targeting the AGO2/miR-185-3p/NRP1 axis may be a potential treatment approach for CRC.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis

et al. 2021

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“…Androgen deprivation therapy (ADT), including surgical or chemical castration, is the backbone of treatment for all stages of recurrent prostate cancer [ 2 ]. Although highly responsive to this therapy initially, eventually almost all patients will evolve into castration-resistant prostate cancer (CRPC) in 18-24 months [ 3 ]. Consequently, the treatment failed, and most patients died from metastasis.…”

Section: Introductionmentioning

confidence: 99%

Loss of exosomal miR-146a-5p from cancer-associated fibroblasts after androgen deprivation therapy contributes to prostate cancer metastasis

Zhao

Ding

et al. 2020

J Exp Clin Cancer Res

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Background Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAFs-derived exosomes involving in metastasis of PCa after ADT. Methods PCa cells were co-cultured with exosomes derived from 10 nM dihydrotestosterone (DHT)-treated (simulating the high androgen level of prostate cancer microenvironment) or ethanol (ETOH) -treated (simulating the castration level of prostate cancer microenvironment after ADT) CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot. Results Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increased migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway. Conclusions CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa.

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“…For example, the RNA binding protein FXR1 degrades p21-mRNA via the stability of miR301a-3p in oral cancer (7). RBP Musashi2 increases the stabilization of the androgen receptor pathway by binding to the 3'-untranslated region of its mRNA, promoting prostate cancer progression (8). EIF2B5 has been proved to participate in cancer progression and has become a biomarker for the prognosis of patients with liver cancer (9).…”

Section: Introductionmentioning

confidence: 99%

Prognostic prediction and gene regulation network of EIF2S2 in hepatocellular carcinoma based on data mining

Ji¹,

Wang²,

Cheng³

et al. 2021

J Gastrointest Oncol

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Background: Hepatocellular carcinoma (HCC) is a malignant tumor with a high fatality rate, predicting poor prognosis and therapeutic effect. Screening potential prognostic genes in HCC could be a creative way to advance clinical treatment. Eukaryotic translation initiation factor 2 subunit beta (EIF2S2) has reportedly been linked to several tumors, including liver cancer, but the prognostic predictions remain unknown.Therefore, we aimed to clarify the prognostic role and interaction network of EIF2S2 in HCC using bioinformatics data.Methods: We screened EIF2S2 using the Oncomine, Ualcan, and TCGA databases. R software was used to analyze the mRNA level and clinicopathological characteristics of hepatocellular carcinoma. Evaluation of the correlations between EIF2S2 and patients' survival was made using the Kaplan-Meier curves and Cox proportional hazards regression model. Then, the influence of EIF2S2 gene mutations on the prognosis of patients was explored by cBioPortal. The protein-protein interaction network of 50 similar genes related to EIF2S2 was implemented by GEPIA2 and Metascape. The LinkedOmics database allowed us to carry out Gene Set Enrichment Analysis. Finally, we constructed the EIF2S2 kinase, miRNA, and transcription factor target networks using GeneMANIA.Results: EIF2S2 mRNA was overexpressed in HCC and was closely associated with clinicopathological features, including gender, age, race, tumor grade, and stage. There was no correlation between EIF2S2 genetic mutations and prognostic survival. Combining Cox proportional hazards regression model analyses, high-expressed EIF2S2 predicted poor prognosis in HCC patients. Additionally, we screened the top three EIF2S2-related genes (PFDN4, HM13, and SNRPD1), the 50 similar genes, and then constructed a 50-similar-gene protein-protein interaction network identified by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using Metascape. EIF2S2 target networks in HCC were identified in kinase, miRNA, and transcription factor networks, including the mitogen-activated protein kinase 1 (MAPK1), miRNAs (Mir-144), and transcription factors (GGAANCGGAANY_UNKNOWN) using GeneMANIA.Conclusions: EIF2S2 plays a crucial role in the gene-regulating network of HCC and may be a potential prognostic marker or therapeutic target for HCC patients.

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RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

Cited by 21 publications

References 54 publications

Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis

Impaired AGO2/miR-185-3p/NRP1 axis promotes colorectal cancer metastasis

Loss of exosomal miR-146a-5p from cancer-associated fibroblasts after androgen deprivation therapy contributes to prostate cancer metastasis

Prognostic prediction and gene regulation network of EIF2S2 in hepatocellular carcinoma based on data mining

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