β-arrestin 2 stimulates degradation of HIF-1α and modulates tumor progression of glioblastoma

Bae, Woom-Yee; Choi, Jae-Sun; Nam, Seungyoon; Jeong, Joo‐Won

doi:10.1038/s41418-021-00802-2

Cited by 19 publications

(9 citation statements)

References 59 publications

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“…The overexpression of β-arrestin 2 in GBM slows HIF-1α signaling, preventing tumor growth and angiogenesis. Conversely, knockdown of β-arrestin 2 increases HIF-1α levels and lessens survival in patients with GBM [ 40 ]. Studies have also indicated that nociceptin receptor (NOPr), a G protein-coupled receptor that is significantly expressed in GBM, mediates nociceptin through the β-arrestin 2/PKC/extracellular signal-regulated kinase 1/2 (Erk1/2) pathway to hinder proliferation, migration, and inflammatory signaling in lipopolysaccharide-stimulated U87 cells [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

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A Novel Splice Variant of BCAS1 Inhibits β-Arrestin 2 to Promote the Proliferation and Migration of Glioblastoma Cells, and This Effect Was Blocked by Maackiain

Kuo

Hung

Tsai

et al. 2022

Cancers

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Brain-enriched myelin-associated protein 1 (BCAS1) is frequently highly expressed in human cancer, but its detailed function is unclear. Here, we identified a novel splice variant of the BCAS1 gene in glioblastoma multiforme (GBM) named BCAS1-SV1. The expression of BCAS1-SV1 was weak in heathy brain cells but high in GBM cell lines. The overexpression of BCAS1-SV1 significantly increased the proliferation and migration of GBM cells, whereas the RNA-interference-mediated knockdown of BCAS1-SV1 reduced proliferation and migration. Moreover, using a yeast-two hybrid assay, immunoprecipitation, and immunofluorescence staining, we confirmed that β-arrestin 2 is an interaction partner of BCAS1-SV1 but not BCAS1. The downregulation of β-arrestin 2 directly enhanced the malignancy of GBM and abrogated the effects of BCAS1-SV1 on GBM cells. Finally, we used a yeast two-hybrid-based growth assay to identify that maackiain (MK) is a potential inhibitor of the interaction between BCAS1-SV1 and β-arrestin 2. MK treatment lessened the proliferation and migration of GBM cells and prolonged the lifespan of tumor-bearing mice in subcutaneous xenograft and intracranial U87-luc xenograft models. This study provides the first evidence that the gain-of-function BCAS1-SV1 splice variant promotes the development of GBM by suppressing the β-arrestin 2 pathway and opens up a new therapeutic perspective in GBM.

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Section: Discussionmentioning

confidence: 99%

“…It has been shown to arrest HIF-1α activity, and the growth and angiogenesis of GBM cells. High β-arrestin 2 expression levels correlate with better survival in patients with GBM [ 40 ]. Thus, BCAS1-SV1 may modify β-arrestin 2 activity to mediate the proliferation and migration of GBM.…”

Section: Introductionmentioning

confidence: 99%

A Novel Splice Variant of BCAS1 Inhibits β-Arrestin 2 to Promote the Proliferation and Migration of Glioblastoma Cells, and This Effect Was Blocked by Maackiain

Kuo

Hung

Tsai

et al. 2022

Cancers

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“…It has been widely accepted that many transcription factors are highly expressed in GBM, including SOX2, HIF-1α, and c-Myc ( Zhang et al, 2011 ; Man et al, 2018 ; Zhou et al, 2016 ; Zheng et al, 2015 ; Bae et al, 2021 ). These transcription factors are not only involved in promoting the initiation of the transcriptional process of protein-coding genes but are also required for the initiative transcription of noncoding genes, including lncRNAs.…”

Section: Generally Molecular Basis Of Lncrnasmentioning

confidence: 99%

Evolving Insights Into the Biological Function and Clinical Significance of Long Noncoding RNA in Glioblastoma

Liu

Chen

Wang

et al. 2022

Front. Cell Dev. Biol.

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Glioblastoma (GBM) is one of the most prevalent and aggressive cancers worldwide. The overall survival period of GBM patients is only 15 months even with standard combination therapy. The absence of validated biomarkers for early diagnosis mainly accounts for worse clinical outcomes of GBM patients. Thus, there is an urgent requirement to characterize more biomarkers for the early diagnosis of GBM patients. In addition, the detailed molecular basis during GBM pathogenesis and oncogenesis is not fully understood, highlighting that it is of great significance to elucidate the molecular mechanisms of GBM initiation and development. Recently, accumulated pieces of evidence have revealed the central roles of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of GBM by binding with DNA, RNA, or protein. Targeting those oncogenic lncRNAs in GBM may be promising to develop more effective therapeutics. Furthermore, a better understanding of the biological function and underlying molecular basis of dysregulated lncRNAs in GBM initiation and development will offer new insights into GBM early diagnosis and develop novel treatments for GBM patients. Herein, this review builds on previous studies to summarize the dysregulated lncRNAs in GBM and their unique biological functions during GBM tumorigenesis and progression. In addition, new insights and challenges of lncRNA-based diagnostic and therapeutic potentials for GBM patients were also introduced.

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“…Promotes cell proliferation and migration potential (Masannat et al, 2018) Bladder cancer Inhibits stem-cell phenotype and enhances chemotherapy response (Kallifatidis et al, 2019) Glioblastoma Obstructs via inhibition of HIF-mediated angiogenesis (Bae et al, 2021) since it has overexpression decreases the expression level of phosphorylated and non-phosphorylated PI3K/AKT and Bcl-2, and increases the appearance level of apoptotic Bax and caspase-3 in cancer cell lines (Y. Jiang et al, 2020).…”

Section: Renal Cancermentioning

confidence: 99%

Deciphering the signaling mechanisms of β‐arrestin1 and β‐arrestin2 in regulation of cancer cell cycle and metastasis

Aamna

Dan

Sahu

et al. 2022

Journal Cellular Physiology

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β‐Arrestins are ubiquitously expressed intracellular proteins with many functions which interact directly and indirectly with a wide number of cellular partners and mediate downstream signaling. Originally, β‐arrestins were identified for their contribution to GPCR desensitization to agonist‐mediated activation, followed by receptor endocytosis and ubiquitylation. However, current investigations have now recognized that in addition to GPCR arresting (hence the name arrestin). β‐Arrestins are adaptor proteins that control the recruitment, activation, and scaffolding of numerous cytoplasmic signaling complexes and assist in G‐protein receptor signaling, thus bringing them into close proximity. They have participated in various cellular processes such as cell proliferation, migration, apoptosis, and transcription via canonical and noncanonical pathways. Despite their significant recognition in several physiological processes, these activities are also involved in the onset and progression of various cancers. This review delivers a concise overview of the role of β‐arrestins with a primary emphasis on the signaling processes which underlie the mechanism of β‐arrestins in the onset of cancer. Understanding these processes has important implications for understanding the therapeutic intervention and treatment of cancer in the future.

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β-arrestin 2 stimulates degradation of HIF-1α and modulates tumor progression of glioblastoma

Cited by 19 publications

References 59 publications

A Novel Splice Variant of BCAS1 Inhibits β-Arrestin 2 to Promote the Proliferation and Migration of Glioblastoma Cells, and This Effect Was Blocked by Maackiain

A Novel Splice Variant of BCAS1 Inhibits β-Arrestin 2 to Promote the Proliferation and Migration of Glioblastoma Cells, and This Effect Was Blocked by Maackiain

Evolving Insights Into the Biological Function and Clinical Significance of Long Noncoding RNA in Glioblastoma

Deciphering the signaling mechanisms of β‐arrestin1 and β‐arrestin2 in regulation of cancer cell cycle and metastasis

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