Abstract
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.
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The datasets generated during the current study are available from the corresponding author on reasonable request.
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This work was supported by Sichuan Medical Scientific Research Youth Innovation Project (No. Q18017) and Scientific Research Foundation of Sichuan Provincial People’s Hospital (No. 2020QN05).
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FFC, YW, and XMW have given substantial contributions to the conception and the design of the manuscript; SYM, YWT, and YM to acquisition, analysis, and interpretation of the data. All authors have participated to drafting the manuscript, FFC, XMY, and ZYL revised it critically. All authors read and approved the final version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Sichuan Provincial People’s Hospital and University of Electronic Science and Technology of China Ethics Committee approved this study. All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all individual participants included in the study.
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Graphical headlights
1. METTL3 promotes the maturation of pri-miR-27a-3p in m6A dependent manner.
2. METTL3 enhances YY1 mRNA stability in an m6A manner.
3. YY1 is identified to be a transcriptional activator for miR-27a-3p.
4. The METTL3/YY1/miR-27a-3p axis affects the proliferation, stemness, and apoptosis MM cells in vivo and in vitro.
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Che, F., Ye, X., Wang, Y. et al. METTL3 facilitates multiple myeloma tumorigenesis by enhancing YY1 stability and pri-microRNA-27 maturation in m6A-dependent manner. Cell Biol Toxicol 39, 2033–2050 (2023). https://doi.org/10.1007/s10565-021-09690-1
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DOI: https://doi.org/10.1007/s10565-021-09690-1