Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11

Zeng, Xing; Chen, Ke; Le, Li; Tian, Jing; Ruan, Weiqiang; Hu, Zhiquan; Peng, Dan; Chen, Zhi

doi:10.1016/j.freeradbiomed.2022.03.031

Cited by 39 publications

(36 citation statements)

References 27 publications

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“…At present, some previous research has demonstrated the function of RBM15 in promoting tumor development, such as clear cell renal cell carcinoma (ccRCC), chronic myeloid leukemia (CML), hepatocellular carcinoma (HCC), and lung cancer. RBM15 is up‐regulated in ccRCC cells, RBM15 can enhance ccRCC cell proliferation, invasion, and migration 28 . Yang et al have reported that RBM15 knockdown inhibits growth and proliferation, promotes apoptosis, and blocks the cell cycle in CML cells 29 .…”

Section: Discussionmentioning

confidence: 99%

“…RBM15 is up-regulated in ccRCC cells, RBM15 can enhance ccRCC cell proliferation, invasion, and migration. 28 Yang et al have reported that RBM15 knockdown inhibits growth and proliferation, promotes apoptosis, and blocks the cell cycle in CML cells. 29 RBM15 is highly expressed in HCC, and increased RBM15 promotes proliferation and invasion of HCC.…”

Section: Discussionmentioning

confidence: 99%

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RBM15 silencing promotes ferroptosis by regulating the TGF‐β/Smad2 pathway in lung cancer

Feng

et al. 2023

Environmental Toxicology

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Objective: We assessed the function and mechanism of RNA binding motif protein 15 (RBM15) silencing in lung cancer development. Methods:The effects of RBM15 knockdown on A549 and H1299 cells were evaluated by MTT, EdU, wound healing, and transwell assay. We then detected the functions of RBM15 silencing on lipid peroxidation, labile iron pool (LIP), ferrous iron (Fe 2+ ), and ferroptosis-related genes. RNA sequencing was performed after RBM15 knockout in lung cancer cells, followed by differentially expressed genes (DEGs), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. Finally, the expression of RBM15 and pathway-related genes was determined by western blot.Results: RBM15 was highly expressed in lung cancer cells. RBM15 silencing reduced the viability, inhibited cell proliferation, invasion, and migration, and suppressed tumor growth in the xenograft mouse model. Knockout of RBM15 regulated ferroptosis-related gene expression. LIP, Fe 2+ , and lipid peroxidation were distinctly increased by the knockout of RBM15. RNA-seq sequencing revealed that there are 367 up-regulated and 368 down-regulated DEGs, which were enriched in molecular functions, biological processes, and cellular components. RBM15 silencing reduced the expression of TGF-β/Smad2, and TGF-β activator (SRI-011381) reversed the inhibitory effect of RBM15 silencing on tumor cell growth. Conclusion:We demonstrated that RBM15 silencing promoted ferroptosis in lung cancer cells by TGF-β/Smad2 pathway, thereby inhibiting lung cancer cell growth, which may provide new light for lung cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

RBM15 silencing promotes ferroptosis by regulating the TGF‐β/Smad2 pathway in lung cancer

Feng

et al. 2023

Environmental Toxicology

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“…Moreover, Wilms tumor 1 associated protein (WTAP), is a conserved protein in the cell nucleus as the partner of Wilms tumor 1 (WT1) ( Little et al, 2000 ), and has been found to correlate with alternative splicing, cell cycle regulation, and X-chromosome inactivation ( Chen et al, 2019 ). RNA binding motif protein 15 (RBM15), whose function is to bind the m6A complex and recruit it to a unique RNA site, also takes part in numerous regulations, including the proliferation and migration of tumor cells, and macrophage infiltration ( Zeng et al, 2022 ). YTH domain containing 1 (YTHDC1), a gene that can bind to m6A-modified RNAs and facilitate the selection of splice site ( Xiao et al, 2016 ), and YTH domain containing 2 (YTHDC2), which is involved in the regulation of mRNA decay ( Lin et al, 2017 ), are members of the YTH family, and play a crucial role in the phase-shift of mitosis and meiosis with different binding affinities of m6A ( He et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity

et al. 2022

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Epilepsy, a functional disease caused by abnormal discharge of neurons, has attracted the attention of neurologists due to its complex characteristics. N6-methyladenosine (m6A) is a reversible mRNA modification that plays essential role in various biological processes. Nevertheless, no previous study has systematically evaluated the role of m6A regulators in epilepsy. Here, using gene expression screening in the Gene Expression Omnibus GSE143272, we identified seven significant m6A regulator genes in epileptic and non-epileptic patients. The random forest (RF) model was applied to the screening, and seven m6A regulators (HNRNPC, WATP, RBM15, YTHDC1, YTHDC2, CBLL1, and RBMX) were selected as the candidate genes for predicting the risk of epilepsy. A nomogram model was then established based on the seven-candidate m6A regulators. Decision curve analysis preliminarily showed that patients with epilepsy could benefit from the nomogram model. The consensus clustering method was performed to divide patients with epilepsy into two m6A patterns (clusterA and clusterB) based on the selected significant m6A regulators. Principal component analysis algorithms were constructed to calculate the m6A score for each sample to quantify the m6A patterns. Patients in clusterB had higher m6A scores than those in clusterA. Furthermore, the patients in each cluster had unique immune cell components and different cell death patterns. Meanwhile, based on the M6A classification, a correlation between epilepsy and glucose metabolism was laterally verified. In conclusion, the m6A regulation pattern plays a vital role in the pathogenesis of epilepsy. The research on m6A regulatory factors will play a key role in guiding the immune-related treatment, drug selection, and identification of metabolism conditions and mechanisms of epilepsy in the future.

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“…Zeng et al. found that EP300 could epigenetically upregulate RBM15 to accelerate clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by driving CXCL11 mRNA m6A modification ( 83 ). These results indicated that BRDs might maintain cancer stemness by directly driving histone acetylation and indirectly regulating m6A methylation.…”

Section: Discussionmentioning

confidence: 99%

Identification of bromodomain-containing proteins prognostic value and expression significance based on a genomic landscape analysis of ovarian serous cystadenocarcinoma

Zhang

Fan

et al. 2022

Front. Oncol.

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BackgroundOvarian serous cystadenocarcinoma (OSC), a common gynecologic tumor, is characterized by high mortality worldwide. Bromodomain (BRD)-containing proteins are a series of evolutionarily conserved proteins that bind to acetylated Lys residues of histones to regulate the transcription of multiple genes. The ectopic expression of BRDs is often observed in multiple cancer types, but the role of BRDs in OSC is still unclear.MethodsWe performed the differential expression, GO enrichment, GSEA, immune infiltration, risk model, subtype classification, stemness feature, DNA alteration, and epigenetic modification analysis for these BRDs based on multiple public databases.ResultsMost BRDs were dysregulated in OSC tissues compared to normal ovary tissues. These BRDs were positively correlated with each other in OSC patients. Gene alteration and epigenetic modification were significant for the dysregulation of BRDs in OSC patients. GO enrichment suggested that BRDs played key roles in histone acetylation, viral carcinogenesis, and transcription coactivator activity. Two molecular subtypes were classified by BRDs for OSC, which were significantly correlated with stemness features, m6A methylation, ferroptosis, drug sensitivity, and immune infiltration. The risk model constructed by LASSO regression with BRDs performed moderately well in prognostic predictions for OSC patients. Moreover, BRPF1 plays a significant role in these BRDs for the development and progression of OSC patients.ConclusionBRDs are potential targets and biomarkers for OSC patients, especially BRPF1.

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Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11

Cited by 39 publications

References 27 publications

RBM15 silencing promotes ferroptosis by regulating the TGF‐β/Smad2 pathway in lung cancer

RBM15 silencing promotes ferroptosis by regulating the TGF‐β/Smad2 pathway in lung cancer

Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity

Identification of bromodomain-containing proteins prognostic value and expression significance based on a genomic landscape analysis of ovarian serous cystadenocarcinoma

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