Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer

Yujiro Nishizawa, Masamitsu Konno, Ayumu Asai, Jun Koseki, Koichi Kawamoto, Norikatsu Miyoshi, Hidekazu Takahashi, Naohiro Nishida, Naotsugu Haraguchi, Daisuke Sakai, Toshihiro Kudo, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii

Research output: Contribution to journalArticle

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Abstract

Recent studies that have emerged on the diversity of RNA modification in tumors suggest their eligibility as bona fide targets in diagnosis and drug discovery. N6- methyladenosine (m6A) was first reported and is most common in epitranscriptome modification of various RNAs. The YT521-B homology (YTH) domain family are representative m6A-binding proteins, but how the YTH domain family is involved in cancer remains to be clearly understood. Given that clinical sequence data in colorectal cancer indicate that overexpression of YTHDF1 is outstanding among other family members, we studied the role of Ythdf1 and the transcriptional control of YTHDF1. Immunostaining of Ythdf1 showed that its expression was associated with various malignant tumor behaviors, such as depth, lymph node metastasis, and poorer cancer stages. The study of patient survival indicated that patients with high Ythdf1 expression had significantly poorer overall survival. The results indicated that Ythdf1 expression is an independent prognostic factor of patients. The in vitro study showed that the knockdown of YTHDF1 resulted in the suppression of cancer proliferation and sensitization to the exposure of anticancer drugs such as fluorouracil and oxaliplatin. Importantly, the study upstream of the YTHDF1 gene indicated that an oncogenic transcription factor c-Myc was associated with YTHDF1 in both expression and chromatin immunoprecipitation data. Moreover, the knockdown experiments of c-Myc showed the inhibition of YTHDF1, supporting a notion of c-Myc-driven YTHDF1 axis significance. These data suggest that m6A reader Ythdf1 plays a significant role in colorectal cancer progression.

Original languageEnglish
Pages (from-to)7476-7486
Number of pages11
JournalOncotarget
Volume9
Issue number7
DOIs
Publication statusPublished - Jan 26 2018

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myc Genes
Colorectal Neoplasms
oxaliplatin
Neoplasms
RNA
Survival
Chromatin Immunoprecipitation
Drug Discovery
Fluorouracil
Carrier Proteins
Transcription Factors
Lymph Nodes
Neoplasm Metastasis
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Nishizawa, Y., Konno, M., Asai, A., Koseki, J., Kawamoto, K., Miyoshi, N., ... Ishii, H. (2018). Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer. Oncotarget, 9(7), 7476-7486. https://doi.org/10.18632/oncotarget.23554

Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer. / Nishizawa, Yujiro; Konno, Masamitsu; Asai, Ayumu; Koseki, Jun; Kawamoto, Koichi; Miyoshi, Norikatsu; Takahashi, Hidekazu; Nishida, Naohiro; Haraguchi, Naotsugu; Sakai, Daisuke; Kudo, Toshihiro; Hata, Taishi; Matsuda, Chu; Mizushima, Tsunekazu; Satoh, Taroh; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi.

In: Oncotarget, Vol. 9, No. 7, 26.01.2018, p. 7476-7486.

Research output: Contribution to journalArticle

Nishizawa, Y, Konno, M, Asai, A, Koseki, J, Kawamoto, K, Miyoshi, N, Takahashi, H, Nishida, N, Haraguchi, N, Sakai, D, Kudo, T, Hata, T, Matsuda, C, Mizushima, T, Satoh, T, Doki, Y, Mori, M & Ishii, H 2018, 'Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer', Oncotarget, vol. 9, no. 7, pp. 7476-7486. https://doi.org/10.18632/oncotarget.23554
Nishizawa Y, Konno M, Asai A, Koseki J, Kawamoto K, Miyoshi N et al. Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer. Oncotarget. 2018 Jan 26;9(7):7476-7486. https://doi.org/10.18632/oncotarget.23554
Nishizawa, Yujiro ; Konno, Masamitsu ; Asai, Ayumu ; Koseki, Jun ; Kawamoto, Koichi ; Miyoshi, Norikatsu ; Takahashi, Hidekazu ; Nishida, Naohiro ; Haraguchi, Naotsugu ; Sakai, Daisuke ; Kudo, Toshihiro ; Hata, Taishi ; Matsuda, Chu ; Mizushima, Tsunekazu ; Satoh, Taroh ; Doki, Yuichiro ; Mori, Masaki ; Ishii, Hideshi. / Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer. In: Oncotarget. 2018 ; Vol. 9, No. 7. pp. 7476-7486.
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AU - Matsuda, Chu

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