RBM15 Functions in Blood Diseases

Hu, Mengyu; Yang, Yi; Ji, Zongfei; Luo, Jianyuan

doi:10.2174/1568009616666160112105706

Cited by 22 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CCND1 gene, which is directly regulated by the EWS-FLI-1 transcription factor [ 41 ], encodes two alternative transcripts of cyclin D1; the common cyclin D1a isoform and a truncated cyclin D1b variant that promotes cellular transformation and prostate cancer progression [ 47 ]. The possibility that RBM11 modulates the splicing of CCND1, and an array of oncogenic genes in EWS, is consistent with known roles for related RNA binding proteins (RBM), including RBM10, RBM15 and RBM25, which alter gene splicing to promote various forms of blood disease and cancer [ 48 , 49 ]. However, because RBM11 is known to promote the alternative splicing of the pro-apoptotic, BCL-X splice variant (BCL-X S ) [ 44 ], it remains unclear how its overexpression may contribute to complex apoptotic signaling in EFT cells.…”

Section: Discussionsupporting

confidence: 54%

A k-mer based transcriptomics approach for antisense drug discovery targeting the Ewing’s family of tumors

et al. 2018

View full text Add to dashboard Cite

Ewing’s sarcoma treatment failures are associated with high mortality indicating a need for new therapeutic approaches. We used a k-mer counting approach to identify cancer-specific mRNA transcripts in 3 Ewing’s Family Tumor (EFT) cell lines not found in the normal human transcriptome. Phosphorodiamidate morpholino oligomers targeting six EFT-specific transcripts were evaluated for cytotoxicity in TC-32 and CHLA-10 EFT lines and in HEK293 renal epithelial control cells. Average morpholino efficacy (EC50) was 0.66 ± 0.13 in TC-32, 0.25 ± 0.14 in CHLA-10 and 3.07 ± 5.02 µM in HEK293 control cells (ANOVA p < 0.01). Synergy was observed for a cocktail of 12 morpholinos at low dose (0.3 µM) in TC-32 cells, but not in CHLA-10 cells. Paired synergy was also observed in both EFT cell lines when the PHGDH pre-mRNA transcript was targeted in combination with XAGE1B or CYP4F22 transcripts. Antagonism was observed when CCND1 was targeted with XAGE1B or CYP4F22, or when IGFBP-2 was targeted with CCND1 or RBM11. This transcriptome profiling approach is highly effective for cancer drug discovery, as it identified new EWS-specific target genes (e.g. CYP4F22, RBM11 and IGBP-2), and predicted effective antisense agents (EC50 < 1 µM) that demonstrate both synergy and antagonism in combination therapy.

show abstract

Section: Discussionsupporting

confidence: 54%

A k-mer based transcriptomics approach for antisense drug discovery targeting the Ewing’s family of tumors

et al. 2018

View full text Add to dashboard Cite

show abstract

“…RBM15 is a member of the SPEN (Split-end) family of proteins, a group of proteins with RNA recognition motifs that functions in transcriptional regulation, post-transcriptional processing and nuclear export of mRNAs (29, 30). RBM15 is highly expressed in the hematopoietic system (29).…”

Section: M6a Deposition Is Required For Aml Cells Survivalmentioning

confidence: 99%

N6-Methyladenosine (m6A): A Promising New Molecular Target in Acute Myeloid Leukemia

2019

View full text Add to dashboard Cite

Recent studies have uncovered an important role for RNA modifications in gene expression regulation, which led to the birth of the epitranscriptomics field. It is now acknowledged that RNA modifiers play a crucial role in the control of differentiation of stem and progenitor cells and that changes in their levels are a relevant feature of different types of cancer. To date, among more than 160 different RNA chemical modifications, the more relevant in cancer biology is the reversible and dynamic N 6 -methylation of adenosine, yielding N 6 -methyladenosine (m 6 A). m 6 A is the more abundant internal modification in mRNA, regulating the expression of the latter at different levels, from maturation to translation. Here, we will describe the emerging role of m 6 A modification in acute myeloid leukemia (AML), which, among first, has demonstrated how mis-regulation of the m6A modifying system can contribute to the development and progression of cancer. Moreover, we will discuss how AML is paving the way to the development of new therapeutic options based on the inhibition of m 6 A deposition.

show abstract

“…Thus, we finally selected RBM15 for further analysis in this study. RBM15 is a member of the split-end (SPEN) family of proteins, which can bind to RNA by interacting with spliceosome components (26,27). RBM15/RBM15B recruit the WTAP-METTL3-METTLE14 RNA methyltransferase complex to install m6A (28).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

Fu¹,

Feng²,

Zhang³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: N6-methyladenosine (m6A) is found in almost all nuclear RNAs of eukaryotes, playing an important and diverse role in many biological processes. Nonetheless, the roles of m6A regulators in abdominal aortic aneurysm (AAA) unknown. Therefore, there is a pressing need to identify m6A RNA methylation regulators in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis.Methods: The GSE98278 dataset were obtained from the Gene Expression Omnibus (GEO) database to perform differential analysis of m6A-related regulators between elective stable abdominal aortic aneurysms (eAAA) and abdominal aortic aneurysm ruptured (rAAA). The random forest model was used to screen candidate m6A regulators to predict the risk of rAAA. The single sample gene set enrichment analysis (ssGSEA) method was then used to evaluate the abundance of 23 immune cells in AAA. The m6A RNA Methylation Quantification Kit was used to measure the total m6A levels of AAA and normal abdominal aorta. The terminal deoxynucleotidyl transferase mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay kit was used to detect the human aortic smooth muscle cells (HASMCs) apoptotic after RBM15 knockdown. Mechanically, RBM15 knockdown was found to reduce the expression of CASP3 in an m6A-dependent manner by Western blotting, RNA immunoprecipitation (RIP), and methylated RNA immunoprecipitation-quantitative polymerase chain reaction (MeRIP-RT-PCR).Results: RBM15, WTAP, ALKBH5, and IGFBP3 were highly expressed in rAAA. In contrast, RBM15B showed opposite results (P<0.05). The high m6A level in the rAAA compared with eAAA and normal abdominal aorta (P<0.05). The random forest model was used to screen 5 candidate m6A regulators to predict the risk of rAAA. Expression of the 5 m6A methylation regulators was validated in AAA samples (P<0.05). RBM15 knockdown inhibited the apoptosis of HASMCs. RBM15 knockdown reduced the expression of CASP3 in an m6A-dependent manner. A strong correlation between the five m6A methylation regulators and immune cell infiltration was identified.Conclusions: In summary, m6A regulators play nonnegligible roles in the occurrence of rAAA. Our investigation of m6A patterns may be able to guide future immunotherapy strategies for AAA.

show abstract

RBM15 Functions in Blood Diseases

Cited by 22 publications

References 0 publications

A k-mer based transcriptomics approach for antisense drug discovery targeting the Ewing’s family of tumors

A k-mer based transcriptomics approach for antisense drug discovery targeting the Ewing’s family of tumors

N6-Methyladenosine (m6A): A Promising New Molecular Target in Acute Myeloid Leukemia

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

Contact Info

Product

Resources

About