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Cited by 283

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RBM15 facilitates laryngeal squamous cell carcinoma progression by regulating TMBIM6 stability through IGF2BP3 dependent

Open access
Wang, Xin, Tian, Linli, Li, Yushan, Wang, Jingting, Yan, Bingrui, Yang, Like, Li, Qiuying, Zhao, Rui, Liu, Ming, Wang, Peng, Sun, Yanan·2021·Journal of Experimental & Clinical Cancer Research

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: Our results revealed the essential roles of RBM15 and IGF2BP3 in m6A methylation modification in LSCC, thus identifying a novel RNA regulatory mechanism.

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Metadata

Authors
Wang, X., Tian, L., Li, Y., Wang, J., Yan, B., Yang, L., Li, Q., Zhao, R., Liu, M., Wang, P., & Sun, Y.
Venue
Journal of Experimental & Clinical Cancer Research
Published
2021-02-26
Volume
40
Issue
1
Pages
80-80
ISSN
  • 0392-9078 (ISSN-L)
  • 1756-9966
OpenAlex
W3129523955
Cited by
283
References
33
FWCI
15.23
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: RBM15 facilitates laryngeal squamous cell carcinoma progression by regulating TMBIM6 stability through IGF2BP3 dependent. https://app.cochat.ai/papers/10.1186/s13046-021-01871-4
The paper
Wang, X., Tian, L., Li, Y., Wang, J., Yan, B., Yang, L., Li, Q., Zhao, R., Liu, M., Wang, P., & Sun, Y. (2021). RBM15 facilitates laryngeal squamous cell carcinoma progression by regulating TMBIM6 stability through IGF2BP3 dependent. Journal of Experimental & Clinical Cancer Research. https://doi.org/10.1186/s13046-021-01871-4

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