Rbm24a Is Necessary for Hair Cell Development Through Regulating mRNA Stability in Zebrafish

Zhang, Yan; Wang, Yanfei; Yao, Xuebo; Wang, Changquan; Chen, Fangyi; Liu, Dong; Shao, Ming; Xu, Zhigang

doi:10.3389/fcell.2020.604026

Cited by 11 publications

(21 citation statements)

References 74 publications

(90 reference statements)

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“…SMPX is a small muscle protein located in the nucleus. It has been reported to be involved in the formation of hearing ( 76 ), but it has not been reported in tumor studies. In this study, we also found that the high expression of these seven genes is related to a poor prognosis in gastric cancer patients, and based on this and previous reports, we speculate that these seven genes can promote the progression of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

et al. 2021

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BackgroundGastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic potential. Gastric cancer has high molecular and phenotypic heterogeneity. New strategies for accurate prognostic evaluation and patient selection for immunotherapy are urgently needed.MethodsWeighted gene coexpression network analysis (WGCNA) was used to identify hub genes related to gastric cancer progression. Based on the hub genes, the samples were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between the subtypes, a gastric cancer risk model was constructed through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The differences in prognosis, clinical features, tumor microenvironment (TME) components and immune characteristics were compared between subtypes and risk groups, and the connectivity map (CMap) database was applied to identify potential treatments for high-risk patients.ResultsWGCNA and screening revealed nine hub genes closely related to gastric cancer progression. Unsupervised clustering according to hub gene expression grouped gastric cancer patients into two subtypes related to disease progression, and these patients showed significant differences in prognoses, TME immune and stromal scores, and suppressive immune checkpoint expression. Based on the different expression patterns between the subtypes, we constructed a gastric cancer risk model and divided patients into a high-risk group and a low-risk group based on the risk score. High-risk patients had a poorer prognosis, higher TME immune/stromal scores, higher inhibitory immune checkpoint expression, and more immune characteristics suitable for immunotherapy. Multivariate Cox regression analysis including the age, stage and risk score indicated that the risk score can be used as an independent prognostic factor for gastric cancer. On the basis of the risk score, we constructed a nomogram that relatively accurately predicts gastric cancer patient prognoses and screened potential drugs for high-risk patients.ConclusionsOur results suggest that the 7-gene signature related to tumor progression could predict the clinical prognosis and tumor immune characteristics of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

et al. 2021

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“…Rbm24 has been identified as a target of ATOH1 and GFI1, key transcription factors required for HC differentiation, through DNA-protein interaction assays and in vivo knockout studies (Cai et al, 2015;Jen et al, 2022). Wholebody deletion of rbm24a in zebrafish embryos disrupted HC morphogenesis and led to hearing and balance deficits (Zhang et al, 2020a;Cheng et al, 2020). Deletion of Rbm24 in 2-monthold mice also resulted in auditory and vestibular dysfunction .…”

Section: Rbm24mentioning

confidence: 99%

Alternative splicing in shaping the molecular landscape of the cochlea

Kim

Koo²,

Bok³

2023

Front. Cell Dev. Biol.

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The cochlea is a complex organ comprising diverse cell types with highly specialized morphology and function. Until now, the molecular underpinnings of its specializations have mostly been studied from a transcriptional perspective, but accumulating evidence points to post-transcriptional regulation as a major source of molecular diversity. Alternative splicing is one of the most prevalent and well-characterized post-transcriptional regulatory mechanisms. Many molecules important for hearing, such as cadherin 23 or harmonin, undergo alternative splicing to produce functionally distinct isoforms. Some isoforms are expressed specifically in the cochlea, while some show differential expression across the various cochlear cell types and anatomical regions. Clinical phenotypes that arise from mutations affecting specific splice variants testify to the functional relevance of these isoforms. All these clues point to an essential role for alternative splicing in shaping the unique molecular landscape of the cochlea. Although the regulatory mechanisms controlling alternative splicing in the cochlea are poorly characterized, there are animal models with defective splicing regulators that demonstrate the importance of RNA-binding proteins in maintaining cochlear function and cell survival. Recent technological breakthroughs offer exciting prospects for overcoming some of the long-standing hurdles that have complicated the analysis of alternative splicing in the cochlea. Efforts toward this end will help clarify how the remarkable diversity of the cochlear transcriptome is both established and maintained.

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“…These defects are correlated with a reduced expression level of several zebrafish orthologs of human deafness genes, including smpx (small muscle protein X-linked), gsdmeb (gasdermin Eb), and otofa (otoferlin a). Further analysis suggests that Rbm24a deficiency leads to reduced stability of the corresponding mRNAs [ 17 , 18 ]. Thus, smpx , gsdmeb , and otofa are possible target mRNAs of Rbm24a for hair cell morphogenesis and function.…”

Section: Rbp-mediated Post-transcriptional Regulation In Inner Ear Ha...mentioning

confidence: 99%

Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration

Shi

Cheng

Saquet

et al. 2022

IJMS

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RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level. They play major roles in the tissue- and stage-specific expression of protein isoforms as well as in the maintenance of protein homeostasis. The inner ear is a bi-functional organ, with the cochlea and the vestibular system required for hearing and for maintaining balance, respectively. It is relatively well documented that transcription factors and signaling pathways are critically involved in the formation of inner ear structures and in the development of hair cells. Accumulating evidence highlights emerging functions of RBPs in the post-transcriptional regulation of inner ear development and hair cell function. Importantly, mutations of splicing factors of the RBP family and defective alternative splicing, which result in inappropriate expression of protein isoforms, lead to deafness in both animal models and humans. Because RBPs are critical regulators of cell proliferation and differentiation, they present the potential to promote hair cell regeneration following noise- or ototoxin-induced damage through mitotic and non-mitotic mechanisms. Therefore, deciphering RBP-regulated events during inner ear development and hair cell regeneration can help define therapeutic strategies for treatment of hearing loss. In this review, we outline our evolving understanding of the implications of RBPs in hair cell formation and hearing disease with the aim of promoting future research in this field.

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Rbm24a Is Necessary for Hair Cell Development Through Regulating mRNA Stability in Zebrafish

Cited by 11 publications

References 74 publications

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

Alternative splicing in shaping the molecular landscape of the cochlea

Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration

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