The neural ELAVL protein HuB enhances endogenous proto-oncogene activation

Hatanaka, Tomoyuki; Higashino, Fumihiro; Tei, Kanchu; Yasuda, Motoaki

doi:10.1016/j.bbrc.2019.07.089

Cited by 8 publications

(8 citation statements)

References 21 publications

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“…In brain tumor and non-small cell lung carcinoma cells, HuB (ELAVL2), the only neural ELAVL protein found to be expressed in cancer cells, was shown to initiate the cytoplasmic translocation of HuR. Afterward, HuB and HuR form a complex in the cytoplasm to enable the stabilization of ARE transcripts by HuR [34]. HuB mRNA is upregulated in primary and metastatic melanoma cell lines compared to NHEMs (GEO: GSE108969) [19].…”

Section: Discussionmentioning

confidence: 99%

HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth

Liebig

Kuphal

Bosserhoff

2020

Cancers

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In addition to genetic changes, post-transcriptional events strongly contribute to the progression of malignant tumors. The RNA-binding protein HuR (ELAVL1) is able to bind and stabilize a large group of target mRNAs, which contain AU-rich elements (ARE) in their 3′-untranslated region. We found HuR to be upregulated in malignant melanoma in vitro and in vivo, significantly correlating with progression in vivo. Additionally, we could show that miR-194-5p can regulate HuR expression level. HuR knockdown in melanoma cells led to the suppression of proliferation and the induction of cellular senescence. Interestingly, HuR overexpression was sufficient to inhibit senescence in BRAFV600E-expressing melanocytes and to force their growth. Here, MITF (Microphthalmia-associated transcription factor), a key player in suppressing senescence and an ARE containing transcript, is positively regulated by HuR. Our results show for the first time that the overexpression of HuR is an important part of the regulatory pathway in the development of malignant melanoma and functions as a switch to overcome oncogene-induced senescence and to support melanoma formation. These newly defined alterations may provide possibilities for innovative therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth

Liebig

Kuphal

Bosserhoff

2020

Cancers

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“…High DDX39A expression is positively correlated with advanced clinical stage and DDX39A activates the Wnt/β-catenin signaling pathway through β-catenin to promote HCC growth, invasion, and metastasis [31] . ELAVL2 activates endogenous proto-oncogenes, causing the progression of a variety of tumors [32] and is involved in tumor resistance to chemotherapy. High ELAVL2 expression may be an independent risk factor for poor chemotherapy response in patients with esophageal squamous cell carcinoma [33] .…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of the Function and Prognostic Value of RNA-Binding Proteins in Hepatocellular Carcinoma

Wu¹,

Yang²,

Yang³

et al. 2020

Preprint

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Background: RNA-binding proteins (RBPs) are abnormally expressed in a variety of malignant tumors and are closely related to tumorigenesis, tumor progression, and prognosis. The role of RBPs in hepatocellular carcinoma (HCC) is unclear. Based on the cancer genome atlas (TCGA) database, we conducted a systematic bioinformatics analysis of abnormally expressed RBPs in HCC, with the aim of identifying the prognostic markers and potential therapeutic targets.Methods: HCC RNA sequencing data downloaded from TCGA database were used to determine the differentially expressed RBPs in livery cancer and normal tissues, followed by performing functional enrichment analysis and visualization of interaction relationships. Univariate and multivariate Cox regression analyses were subsequently used to identify RBPs that were significantly related to the prognosis to construct a prognostic model. The predictive performance of the prognostic model was evaluated by survival analysis and receiver operating characteristic (ROC) curve analysis and verified in the test cohort. Human protein atlas online database was used to verify the expression level of RBPs in the prognostic model.Results: In total, 82 differentially expressed RBPs were identified, including 55 upregulated and 27 downregulated RBPs. Further functional enrichment and interaction analyses showed that the differentially expressed RBPs were mainly related to regulating of mRNA metabolic process, RNA catabolic, mRNA catabolic process, and macromolecule methylation. Five RBP genes, LIN28B, SMG5, PPARGC1A, LARP1B, and ANG were identified as prognostic-related genes and used to construct the prognostic model. The predictive ability of the prognostic model was verified in the test cohort. ROC curve analysis showed that the prognostic model had good sensitivity and specificity. Independent prognostic analysis showed that the risk score may be an independent prognostic factor for HCC.Conclusion: This study constructed a reliable prognostic prediction model by analyzing the differentially expressed RBPs of HCC, facilitating the identification of HCC prognostic biomarkers and therapeutic targets.

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“…There are also notable cancer-related interactions between members of the ELAVL family. A combination of ELAVL2 and ELAVL1 has been shown to localize to the nucleus and to be indispensable in the activation of several proto-oncogenes, including v-fos, v-ets, and v-myc ( Hatanaka et al, 2019 ). Also, by binding with a structure containing an AU-rich sequence, ELAVL2 and ELAVL4 together inhibit the assembly of the core complex of telomerase to reduce its activity and cell growth in human neuroblastoma cells; notably, the activity of this complex antagonizes the function of ELAVL1 ( Cheng et al, 2021 ).…”

Section: Elavl Proteins In Pathological and Physiological Processesmentioning

confidence: 99%

Roles of Embryonic Lethal Abnormal Vision-Like RNA Binding Proteins in Cancer and Beyond

Cai

Zheng

Yao

et al. 2022

Front. Cell Dev. Biol.

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Embryonic lethal abnormal vision-like (ELAVL) proteins are RNA binding proteins that were originally discovered as indispensable regulators of the development and functioning of the nervous system. Subsequent studies have shown that ELAVL proteins not only exist in the nervous system, but also have regulatory effects in other tissues. ELAVL proteins have attracted attention as potential therapeutic targets because they stabilize multiple mRNAs by binding within the 3′-untranslated region and thus promote the development of tumors, including hepatocellular carcinoma, pancreatic cancer, ovarian cancer, breast cancer, colorectal carcinoma and lung cancer. Previous studies have focused on these important relationships with downstream mRNAs, but emerging studies suggest that ELAVL proteins also interact with non-coding RNAs. In this review, we will summarize the relationship of the ELAVL protein family with mRNA and non-coding RNA and the roles of ELAVL protein family members in a variety of physiological and pathological processes.

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The neural ELAVL protein HuB enhances endogenous proto-oncogene activation

Cited by 8 publications

References 21 publications

HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth

HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth

Systematic Analysis of the Function and Prognostic Value of RNA-Binding Proteins in Hepatocellular Carcinoma

Roles of Embryonic Lethal Abnormal Vision-Like RNA Binding Proteins in Cancer and Beyond

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