METTL3 facilitates multiple myeloma tumorigenesis by enhancing YY1 stability and pri-microRNA-27 maturation in m6A-dependent manner.

Multiple myeloma (MM) is a pernicious plasma cell disorder and has a poor prognosis. N6-methyladenosine (m6A) is an abundant epigenetic RNA modification and is important in cancer progression. Nevertheless, the function of m6A and its regulator METTL3 in MM are rarely reported. Here, we identified the m6A "writers", METTL3, was enhanced in MM and found that Yin Yang 1 (YY1) and primary-miR-27a-3p were the potential target for METTL3. METTL3 promoted primary-miR-27a-3p maturation and YY1 mRNA stability in an m6A manner. YY1 also was found to facilitate miR-27a-3p transcription. METTL3 affected the growth, apoptosis, and stemness of MM cells through accelerating the stability of YY1 mRNA and the maturation of primary-miR-27a-3p in vitro and in vivo. Our results reveal the key function of the METTL3/YY1/miR-27a-3p axis in MM and may provide fresh insights into MM therapy.