The association of
RNA modification in
cancer has recently been highlighted.
Methyltransferase like 8 (METTL8) is an
enzyme and its role in
mRNA m3C modification has barely been studied. In this study, we found that METTL8 expression was significantly up-regulated in canine mammary
tumor and investigated its functional roles in the
tumor process, including
cancer cell proliferation and migration. METTL8 expression was up-regulated in most human
breast cancer cell lines tested and decreased by Yin Yang 1 (
YY1) transcription factor knockdown, suggesting that YY1 is a regulating
transcription factor. The knockdown of METTL8 attenuated
tumor cell growth and strongly blocked
tumor cell migration. AT-rich interactive domain-containing
protein 1A (ARID1A) was identified as a candidate
mRNA by METTL8. ARID1A
mRNA binds to METTL8
protein. ARID1A
mRNA expression was not changed by METTL8 knockdown, but ARID1A
protein level was significantly increased. Collectively, our study indicates that METTL8 up-regulated by YY1 in
breast cancer plays an important role in
cancer cell migration through the
mRNA modification of ARID1A, resulting in the attenuation of its translation.