Cited by 27RNA modifications and cancerRNA Research and SplicingRNA regulation and disease

TTC22 promotes m6A-mediated WTAP expression and colon cancer metastasis in an RPL4 binding-dependent pattern

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You, Abin, Tian, Wei, Yuan, Hongfan, Gu, Liankun, Zhou, Jing, Deng, Dajun·2022·Oncogene

Published version of a preprint

Abstract

Abstract WTAP, an essential component of the RNA N-6-methyladenosine (m6A) modification complex, guides METLL3-METLL14 heteroduplexes to target RNAs in the nuclear speckles of mammalian cells. Here, we show that TTC22 is widely coexpressed with WTAP and FTO in many human tissues by mining Genotype-Tissue Expression (GTEx) datasets. Our results indicate that the direct interaction of TTC22 with 60S ribosomal protein L4 (RPL4) promotes the binding of WTAP mRNA to RPL4, enhances the stability and translation efficiency of WTAP mRNA, and consequently increases the level of WTAP protein. Also, WTAP mRNA itself is an m6A target and YTHDF1 is characterized as an essential m6A binding protein in WTAP mRNA. TTC22 triggers a positive feedback loop between WTAP expression and WTAP mRNA m6A modification, leading to an increased m6A level in total RNA. The knockdown of RPL4, WTAP, or YTHDF1 expression diminishes the TTC22-induced increase in the m6A level of total RNA. Thus, TTC22 caused dramatic expression changes in genes related to metabolic pathways, ribosomal biogenesis, the RNA spliceosome, and microorganism infections. Importantly, TTC22 upregulates the expression of SNAI1 by increasing m6A level and thus promotes lung metastases of colon cancer cells in mice. In conclusion, our study showed that TTC22 upregulates WTAP and SNAI1 expression, which contributes to TTC22-induced colon cancer metastasis.

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Authors
You, A., Tian, W., Yuan, H., Gu, L., Zhou, J., & Deng, D.
Affiliations
  • Xiamen University (CN)
  • Peking University Cancer Hospital (CN)
Corresponding author
  • Tian, Wei
  • Deng, Dajun
Venue
Oncogene
Published
2022-07-07
Volume
41
Issue
32
Pages
3925-3938
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W4284665171
Cited by
27
References
44
Citations by year
2026: 7 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 1
FWCI
1.63
Type
journal article
Language
en
Open access
Locations
  • Oncogene (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
  • Figshare (cc-by)
Funders
  • National Natural Science Foundation of China (81372592)
  • Peking University
  • Fundamental Research Funds for the Central Universities
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
WTAP, RNA N6-methyladenosine, m6A RNA methylation, ribosomal protein L4, YTHDF1, SNAI1, colon cancer metastasis, lung metastasis, mRNA stability, translation efficiency, positive feedback loop, FTO
MeSH terms
Alpha-Ketoglutarate-Dependent Dioxygenase FTO, RNA Splicing Factors, Animals, Colonic Neoplasms, Humans, Lung Neoplasms, Mammals, Ribosomal Proteins, RNA, Messenger, Cell Cycle Proteins, Mice

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