Down‐regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR‐432‐5p/β‐catenin feedback loop

Zhang, Yanping; Liu, Kailong; Wang, Yaxuan; Yang, Zhan; Han, Zhenwei; Lu, Bao‐Sai; Qi, Ji; Yin, Yuewei; Teng, Zhihai; Xueliang, Chang; Li, Jingdong; Xiao, Hong; Li, Wei

doi:10.1096/fj.201900537r

Cited by 30 publications

(31 citation statements)

References 49 publications

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“…The function of RBM5 in neurogenesis is poorly understood (Jackson & Kochanek 2020), although its roles in apoptosis and tumour suppression (Xu et al 2019; Zhang et al 2019; Sutherland et al 2010; Bechara et al 2013) and spermatogenesis (O’Bryan et al 2013) are well documented. We show a clear switch from a truncated, non-coding RBM5 isoform ENST00000474470 to the full-length coding isoform ENST00000347869 during differentiation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes

Wright

Hall

Irish

et al. 2021

Preprint

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Alternative splicing (AS) is a key mechanism underlying cellular differentiation and a driver of complexity in mammalian neuronal tissues. However, understanding of which isoforms are differentially used or expressed and how this affects cellular differentiation remains unclear. Long read sequencing allows full-length transcript recovery and quantification, enabling transcript-level analysis of AS processes and how these change with cell state. Here, we utilise Oxford Nanopore Technologies sequencing to produce a custom annotation of a well-studied human neuroblastoma cell line and to characterise isoform expression and usage across differentiation. We identify many previously unannotated features, including a novel transcript of the voltage-gated calcium channel subunit gene, CACNA2D2. We show differential expression and usage of transcripts during differentiation, and identify a putative molecular regulator underlying this state change. Our work highlights the potential of long read sequencing to uncover previously unknown transcript diversity and mechanisms influencing alternative splicing.

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Section: Resultsmentioning

confidence: 99%

Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes

Wright

Hall

Irish

et al. 2021

Preprint

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“…Biotin-labeled RNA was synthesized via in vitro transcription as previously described 3 . The RBM24 3′ UTR containing T7 promoter sequences was amplified with or without Biotin-16-UTP (Ambion, AM8452) by using the MEGAscript T7 Transcription Kit (Ambion, AM1334).…”

Section: Methodsmentioning

confidence: 99%

“…Among these cases, approximately 70% of new cases are nonmuscle-invasive BC (NMIBC), while 30% are muscle-invasive BC (MIBC) 2 . Surgery, chemotherapy, and radiation therapy are the main treatments for BC patients 3 . However, the 5-year survival rate of high-risk patients is still very low, and the current main treatment methods cannot prevent the recurrence or progression of these BC patients 4 .…”

Section: Introductionmentioning

confidence: 99%

“…Using immunoprecipitation coupled to reverse transcription and microarray analysis (RIP-ChIP), Yu et al demonstrated that RBM24 is a multitasking RNA-binding protein (RBP) capable of regulating the stability and expression of multiple bound targets 10 . RBPs may function as suppressors or facilitators of disease depending on the specific upstream regulators and downstream effectors (targets) 3 . However, the role of RBM24 in BC is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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RBM24 exacerbates bladder cancer progression by forming a Runx1t1/TCF4/miR-625-5p feedback loop

Yin

Liu

et al. 2021

Exp Mol Med

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RNA–binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development by regulating premRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remain unclear. In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that a higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted BC cell proliferation, while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanistically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and suppressing the transcription of miR-625-5p, which directly targets RBM24 and suppresses RBM24 expression. RBM24-regulated BC cell proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop. These results indicate that the RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop participates in BC progression. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.

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“…For example, miR-432-3p was highly expressed in the ESCC tumors compared with that in the corresponding non-cancerous esophageal mucosa, and up-regulated miR-432 could decrease sensitivity of the cancer cells to chemotherapeutic drugs 15 . MiR-432 has also been reported to play an important role in tumor progression; it can suppress tumor growth, but also promote tumor progression by regulating cell proliferation and apoptosis 16 . In PCNSL, the expression and role of miR-432 remains unclear; our study is the first to demonstrate up-regulated miR-432 in patients with PCNSL.…”

Section: Discussionmentioning

confidence: 99%

miR-432 is a novel biomarker for PCNSL and is associated with cell adhesion: An integrated bioinformatics analysis

Ma¹

2020

Preprint

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Background: Primary central nervous system lymphoma (PCNSL), a rare form of the non-Hodgkin's lymphoma (NHL), usually has a poor prognosis, and molecular pathogenesis of PCNSL has not been fully elucidated. Here, potential miRNA biomarkers were investigated in patients with PCNSL using an integrated bioinformatics analysis. Methods: Expression profile arrays (GSE122011, GSE139031, and GSE25297) were obtained from the Gene Expression Omnibus (GEO). Free-scale miRNA co-expression networks were constructed with 27 PCNSL patients from GSE122011 by the weighted gene co-expression network analysis (WGCNA) in order to identify candidate biomarkers. Subsequently, miRNA-miRNA networks were visualized with the Cytoscape. Expression of candidate miRNAs was assessed in serum samples from GSE139031, including 42 PCNSL patients and 77 non-cancer individuals, and the sensitivity and the specificity were assessed by the receiver operating characteristic (ROC) curve. From GSE25297, differentially expressed genes (DEGs) from the PCNSL tissues (n = 7) and the normal lymph nodes (n = 7) were compared, target genes of candidate miRNAs were downloaded from TargetScan database, and target genes that were also down-regulated in GSE25297 were used to construct the protein-protein interaction (PPI) networks and for the gene ontology (GO) analysis. Results: miRNAs were clustered into two groups with 8 modules in 27 patients with PCNSL. One group consisted of the yellow and the turquoise modules, and the second group consisted of the other six modules. In the miRNA-miRNA network, the highest nodes were observed between miR-432 and miR-330-3p, which were from the yellow and the turquoise modules, and only miR-432 was closely associated with both the yellow (0.977, P = 2.88E -18 ) and the turquoise modules (0.525, P = 0.005). Additionally, patients with PCNSL had higher serum miR-432 expression compared with that in the non-cancer controls in GSE139031, and miR-432 has a higher accuracy for discriminating between PCNSL and non-cancer samples (AUC: 0.77; 95% CI: 0.6923 to 0.8550). For target genes of miR-432, RASGRF , DGKG , SMIM22 , SPOCD1 , NRCAM , CNTN2 , PTPRD , POTED , IGSF3 , SLC24A2 , CTNND2 , AIF1L , TMEM229A , GLDN , and MOBP were down-regulated in the PCNSL tissues. Among them, CTNND2 , GLDN , NRCAM , and PTPRD were associated with cell adhesion. Conclusion: Up-regulated miR-432 expression is a novel biomarker for patients with PCNSL and may be associated with cell adhesion.

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Down‐regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR‐432‐5p/β‐catenin feedback loop

Cited by 30 publications

References 49 publications

Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes

Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes

RBM24 exacerbates bladder cancer progression by forming a Runx1t1/TCF4/miR-625-5p feedback loop

miR-432 is a novel biomarker for PCNSL and is associated with cell adhesion: An integrated bioinformatics analysis

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