Abstract
N6-methyladenosine modification is the most common RNA modification mechanism in mammals. YTHDF1, a m6A reader, can recognize the m6A of mRNAs to facilitate the interaction with the mRNA ribosome assembly and recruitment of translation initiators to promote translation. From a clinical perspective, YTHDF1 upregulation is frequently observed in breast cancer, but its involvement in those cancer-related events is still unclear. Here we report that YTHDF1 is a cancer driver capable of facilitating the proliferation and invasion of breast cancer cells as well as enhancing tumorigenicity and metastasis through promoting glycolysis. We found that tumor hypoxia can transcriptionally induce HIF1α and post-transcriptionally inhibit the expression of miR-16-5p to promote YTHDF1 expression, which could sequentially enhance tumor glycolysis by upregulating PKM2 and eventually increase the tumorigenesis and metastasis potential of breast cancer cells. Inhibiting YTHDF1 via gene knockdown or miR-16-5p would significantly abolish YTHDF1-dependent tumor growth and metastasis. In summary, we identified the role of the YTHDF1-PKM2 signal axis in the occurrence and development of breast cancer, which can be used as a potential target for breast cancer treatment.