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 language | English |
|---|---|
| Pages (from-to) | 7476-7486 |
| Number of pages | 11 |
| Journal | Oncotarget |
| Volume | 9 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jan 26 2018 |
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All Science Journal Classification (ASJC) codes
- Oncology
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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 journal › Article
}
TY - JOUR
T1 - Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer
AU - Nishizawa, Yujiro
AU - Konno, Masamitsu
AU - Asai, Ayumu
AU - Koseki, Jun
AU - Kawamoto, Koichi
AU - Miyoshi, Norikatsu
AU - Takahashi, Hidekazu
AU - Nishida, Naohiro
AU - Haraguchi, Naotsugu
AU - Sakai, Daisuke
AU - Kudo, Toshihiro
AU - Hata, Taishi
AU - Matsuda, Chu
AU - Mizushima, Tsunekazu
AU - Satoh, Taroh
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
PY - 2018/1/26
Y1 - 2018/1/26
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85040996326&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.23554
DO - 10.18632/oncotarget.23554
M3 - Article
AN - SCOPUS:85040996326
VL - 9
SP - 7476
EP - 7486
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 7
ER -