General Information of the m6A Regulator (ID: REG00021)
Regulator Name RNA-binding motif protein 15B (RBM15B)
Synonyms
One-twenty two protein 3; HsOTT3; HuOTT3; Putative RNA-binding protein 15B; OTT3
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Gene Name RBM15B
Sequence
MKRQSERDSSPSGRGSSSSAKRPREREREAEAGGRRAAHKASGGAKHPVPARARDKPRGS
GSGGGGHRDGRGTGDANHRASSGRSSGSGAGGGGRGGKASGDPGASGMSPRASPLPPPPP
PPGAEPACPGSSAAAPEYKTLLISSLSPALPAEHLEDRLFHQFKRFGEISLRLSHTPELG
RVAYVNFRHPQDAREARQHALARQLLLYDRPLKVEPVYLRGGGGSSRRSSSSSAAASTPP
PGPPAPADPLGYLPLHGGYQYKQRSLSPVAAPPLREPRARHAAAAFALDAAAAAAVGLSR
ERALDYYGLYDDRGRPYGYPAVCEEDLMPEDDQRATRNLFIGNLDHSVSEVELRRAFEKY
GIIEEVVIKRPARGQGGAYAFLKFQNLDMAHRAKVAMSGRVIGRNPIKIGYGKANPTTRL
WVGGLGPNTSLAALAREFDRFGSIRTIDHVKGDSFAYIQYESLDAAQAACAKMRGFPLGG
PDRRLRVDFAKAEETRYPQQYQPSPLPVHYELLTDGYTRHRNLDADLVRDRTPPHLLYSD
RDRTFLEGDWTSPSKSSDRRNSLEGYSRSVRSRSGERWGADGDRGLPKPWEERRKRRSLS
SDRGRTTHSPYEERSRTKGSGQQSERGSDRTPERSRKENHSSEGTKESSSNSLSNSRHGA
EERGHHHHHHEAADSSHGKKARDSERNHRTTEAEPKPLEEPKHETKKLKNLSEYAQTLQL
GWNGLLVLKNSCFPTSMHILEGDQGVISSLLKDHTSGSKLTQLKIAQRLRLDQPKLDEVT
RRIKQGSPNGYAVLLATQATPSGLGTEGMPTVEPGLQRRLLRNLVSYLKQKQAAGVISLP
VGGSKGRDGTGMLYAFPPCDFSQQYLQSALRTLGKLEEEHMVIVIVRDTA
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Family RRM Spen family
Function
RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA. Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex. Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist. Functions in the regulation of alternative or illicit splicing, possibly by regulating m6A methylation. Inhibits pre-mRNA splicing. Also functions as a mRNA export factor by acting as a cofactor for the nuclear export receptor NXF1.
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Gene ID 29890
Uniprot ID
RB15B_HUMAN
Regulator Type WRITER ERASER READER
Mechanism Diagram Click to View the Original Diagram
Target Genes Click to View Potential Target Genes of This Regulator
Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)
RBM15B can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.
Browse Target Gene related Disease
Browse Target Gene related Drug
Putative C->U-editing enzyme APOBEC-4 (APOBEC4)
Ovarian cancer [ICD-11: 2C73]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [1]
Responsed Disease Ovarian cancer [ICD-11: 2C73]
In-vitro Model
HEY Ovarian serous adenocarcinoma Homo sapiens CVCL_0297
THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
Response Summary Putative C->U-editing enzyme APOBEC-4 (APOBEC4) was found to be significantly correlated with m6A regulators such as WTAP, METTL14, ZC3H13, RBM15B, and FMR1. APOBEC3A was identified as a protective factor from comprehensive analyses based on the immune microenvironment and genomic instability of ovarian cancer. APOBEC3A had the potential to serve as a promising prognostic biomarker for foretelling the survival and immunotherapy response of ovarian cancer patients.
Translocating chain-associated membrane protein 2 (TRAM2)
Liver cancer [ICD-11: 2C12]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug Sorafenib Approved
Target Regulation Up regulation
In-vitro Model
SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2.215 (Hep-G2.215 were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences)
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
7721 (Human hepatic malignant cell line)
In-vivo Model HCC-LM3 cells transfected with sh-NC and sh-RBM15B-3 were injected into the axilla or tail vein of mice.
Response Summary Overexpression of RBM15B promotes HCC cell proliferation and invasion and induces sorafenib resistance in HCC cells. RBM15B is transcriptionally activated by YY1 and regulates the stability of Translocating chain-associated membrane protein 2 (TRAM2) mRNA in an m6A-dependent manner.
Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)
Colon cancer [ICD-11: 2B90]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [3]
Responsed Disease Colon adenocarcinoma [ICD-11: 2B90.Y]
Target Regulation Up regulation
In-vitro Model
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
HT29 Colon cancer Mus musculus CVCL_A8EZ
In-vivo Model To develop the syngeneic model, 1 × 106 MC38-Ctrl or MC38-Gpx4KD cells were injected subcutaneously into the right flank of C57BL/6 mice.
Proliferating cell nuclear antigen (PCNA)
Prostate cancer [ICD-11: 2C82]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [4]
Responsed Disease Prostate cancer [ICD-11: 2C82]
Target Regulation Down regulation
In-vitro Model
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
DU145 Prostate carcinoma Homo sapiens CVCL_0105
22Rv1 Prostate carcinoma Homo sapiens CVCL_1045
RWPE-1 Normal Homo sapiens CVCL_3791
In-vivo Model The mice were kept under standard conditions and provided with care in accordance with established protocols. For the experiment, 1 × 106 DU145 cells with reduced RBM15B expression and corresponding control cells were injected subcutaneously into the right flank of each nude mouse. Tumor length (L) and width (W) were measured weekly, and tumor volume was calculated using the formula: Volume = (W2 × L) / 2. Four weeks following the injections, mice were euthanized by intraperitoneal administration of sodium pentobarbital at a dose of 150 mg/kg. Tumors were then surgically removed and weighed.
Unspecific Target Gene
Liver cancer [ICD-11: 2C12]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [5]
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug Teniposide Approved
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
mTOR signaling pathway hsa04150
Cell Process DNA repair
In-vitro Model
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
In-vivo Model To establish a tumour model, C57BL/6 mice were intraperitoneal injected with 25 mg/kg diethylnitrosamine at 2 weeks of age.
Response Summary The m6A model includes LRPPRC, YTHDF2, KIAA14219, and RBM15B, classified A-hepatocellular carcinoma patients into high/low-risk subtypes. The expression of Immunosuppressive cytokines DNMT1/EZH2 was up-regulated in A-hepatocellular carcinoma patients, and teniposide can be a potential therapeutic drug for A-hepatocellular carcinoma.
Coronary artery disease [ICD-11: BA8Z]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [6]
Responsed Disease Coronary artery disease [ICD-11: BA8Z]
In-vitro Model
HUVEC-CS
N.A. Homo sapiens CVCL_0F27
Translocating chain-associated membrane protein 2 (TRAM2)
Sorafenib [Approved]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene [2]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
Target Regulation Up regulation
In-vitro Model SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2.215 (Hep-G2.215 were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences)
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
7721 (Human hepatic malignant cell line)
In-vivo Model HCC-LM3 cells transfected with sh-NC and sh-RBM15B-3 were injected into the axilla or tail vein of mice.
Response Summary Overexpression of RBM15B promotes HCC cell proliferation and invasion and induces sorafenib resistance in HCC cells. RBM15B is transcriptionally activated by YY1 and regulates the stability of Translocating chain-associated membrane protein 2 (TRAM2) mRNA in an m6A-dependent manner.
Unspecific Target Gene
Teniposide [Approved]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene [5]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
mTOR signaling pathway hsa04150
Cell Process DNA repair
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
In-vivo Model To establish a tumour model, C57BL/6 mice were intraperitoneal injected with 25 mg/kg diethylnitrosamine at 2 weeks of age.
Response Summary The m6A model includes LRPPRC, YTHDF2, KIAA14219, and RBM15B, classified A-hepatocellular carcinoma patients into high/low-risk subtypes. The expression of Immunosuppressive cytokines DNMT1/EZH2 was up-regulated in A-hepatocellular carcinoma patients, and teniposide can be a potential therapeutic drug for A-hepatocellular carcinoma.
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Regulator
RNA modification
m6A Target: Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)
In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00014
Epigenetic Regulator 28S rRNA (cytosine-C(5))-methyltransferase (NSUN5)
Regulated Target Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)
Crosstalk relationship m5C → m6A
Disease Colon cancer
References
Ref 1 Comprehensive Analyses Identify APOBEC3A as a Genomic Instability-Associated Immune Prognostic Biomarker in Ovarian Cancer. Front Immunol. 2021 Oct 21;12:749369. doi: 10.3389/fimmu.2021.749369. eCollection 2021.
Ref 2 YY1-Targeted RBM15B Promotes Hepatocellular Carcinoma Cell Proliferation and Sorafenib Resistance by Promoting TRAM2 Expression in an m6A-Dependent Manner. Front Oncol. 2022 Apr 14;12:873020. doi: 10.3389/fonc.2022.873020. eCollection 2022.
Ref 3 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. doi: 10.1038/nrd4545.
Ref 4 Becatecarin (rebeccamycin analog, NSC 655649) is a transport substrate and induces expression of the ATP-binding cassette transporter, ABCG2, in lung carcinoma cells. Cancer Chemother Pharmacol. 2009 Aug;64(3):575-83.
Ref 5 Identification and Characterization of Alcohol-related Hepatocellular Carcinoma Prognostic Subtypes based on an Integrative N6-methyladenosine methylation Model. Int J Biol Sci. 2021 Aug 14;17(13):3554-3572. doi: 10.7150/ijbs.62168. eCollection 2021.
Ref 6 Molecular and cellular pharmacology of the novel noncamptothecin topoisomerase I inhibitor Genz-644282. Mol Cancer Ther. 2011 Aug;10(8):1490-9.