RBM15 facilitates laryngeal squamous cell carcinoma progression by regulating TMBIM6 stability through IGF2BP3 dependent
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Open Access
- 26 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Experimental & Clinical Cancer Research
- Vol. 40 (1), 1-18
- https://doi.org/10.1186/s13046-021-01871-4
Abstract
Laryngeal cancer has the highest mortality rate among head and neck tumours. RNA N6-methyladenosine (m6A) is the most plentiful and variable in mammalian mRNA. Yet, the m6A regulatory mechanism underlying the carcinogenesis or progression of LSCC remains poorly understood. The m6A RNA methylation quantification kit was used to detect tissue methylation levels. m6A microarray analysis, mRNA transcriptomic sequencing (mRNA-seq), and proteomics were used to determine RBM15, TMBIM6, and IGF2BP3. Immunohistochemical (IHC), quantitative real-time PCR (qRT-PCR) and Western blot were used to investigate RBM15, TMBIM6, and IGF2BP3 expression in tissue samples and cell lines. The biological effects of RBM15 were detected both in vitro and in vivo. The combination relationship between RBM15/IGF2BP3 and TMBIM6 was verified by RNA immunoprecipitation (RIP) assay, Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNase Mazf, and luciferase report assay. RNase Mazf was used to determine the methylation site on TMBIM6 mRNA. Hoechst staining assay was used to confirm the apoptotic changes. The actinomycin D verified TMBIM6 stability. The global mRNA m6A methylation level significantly increased in LSCC patients. RBM15, as a “writer” of methyltransferase, was significantly increased in LSCC and was associated with unfavorable prognosis. The knockdown of RBM15 reduced the proliferation, invasion, migration, and apoptosis of LSCC both in vitro and in vivo. The results were reversed after overexpressing RBM15. Mechanically, TMBIM6 acted as a downstream target of RBM15-mediated m6A modification. Furthermore, RBM15-mediated m6A modification of TMBIM6 mRNA enhanced TMBIM6 stability through IGF2BP3-dependent. Our results revealed the essential roles of RBM15 and IGF2BP3 in m6A methylation modification in LSCC, thus identifying a novel RNA regulatory mechanism.Keywords
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Funding Information
- National Natural Science Foundation of China (81772874, 81272965)
- Postdoctoral Research Foundation of China (2020M670926)
This publication has 41 references indexed in Scilit:
- Identification and Validation of Reference Genes for RT-qPCR Studies of Hypoxia in Squamous Cervical Cancer PatientsPLOS ONE, 2016
- Bax inhibitor-1 is overexpressed in non-small cell lung cancer and promotes its progression and metastasis.2015
- The dynamic epitranscriptome: N6-methyladenosine and gene expression controlNature Reviews Molecular Cell Biology, 2014
- Magnetic resonance for laryngeal cancerCurrent Opinion in Otolaryngology & Head and Neck Surgery, 2014
- Laryngeal cancerCurrent Opinion in Otolaryngology & Head and Neck Surgery, 2014
- Cancer statistics, 2014CA: A Cancer Journal for Clinicians, 2014
- SOX2 overexpression correlates with poor prognosis in laryngeal squamous cell carcinomaAuris Nasus Larynx, 2013
- Lentivirus-Mediated RNA Interference Targeting Bax Inhibitor-1 Suppresses Ex Vivo Cell Proliferation and In Vivo Tumor Growth of Nasopharyngeal CarcinomaHuman Gene Therapy, 2011
- Expression and functional analysis of Bax inhibitor‐1 in human breast cancer cellsThe Journal of Pathology, 2005
- Interaction of the Epstein-Barr Virus mRNA Export Factor EB2 with Human Spen Proteins SHARP, OTT1, and a Novel Member of the Family, OTT3, Links Spen Proteins with Splicing Regulation and mRNA ExportPublished by Elsevier BV ,2005