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.