Methyltransferase　N6-adenosine　(METTL5)　is　a　methyltransferase　that　specifically　catalyzes　18S　rRNA　N6　methylation　at　adenosine　1832　(m(6)A(1832)),　which　is　located　in　a　critical　position　in　the　decoding　center,　therefore　suggesting　its　potential　importance　in　the　regulation　of　translation.　However,　the　underlying　mechanism　of　METTL5-mediated　translation　regulation　of　specific　genes　and　its　biological　functions　are　largely　undefined.　To　the　best　of　our　knowledge,　the　present　study　demonstrated　for　the　first　time　that　METTL5　was　an　oncogene　that　promoted　cell　proliferation,　migration,　invasion　and　tumorigenesis　in　pancreatic　cancer.　In　addition,　the　oncogenic　function　of　METTL5　may　involve　an　increase　in　c-Myc　translation,　as　evidenced　by　the　fact　that　the　oncogenic　effect　caused　by　METTL5　overexpression　could　be　abolished　by　c-Myc　knockdown.　Notably,　m(6)A　modifications　at　the　5　＇　untranslated　region　(5　＇　UTR)　and　coding　DNA　sequence　region　(near　the　5　＇　UTR)　of　c-Myc　mRNA　played　a　critical　role　in　the　specific　translation　regulation　by　METTL5.　In　addition,　it　was　further　demonstrated　that　METTL5　and　its　cofactor　tRNA　methyltransferase　activator　subunit　11-2　synergistically　promote　pancreatic　cancer　progression.　These　findings　revealed　important　roles　for　METTL5　in　the　development　of　pancreatic　cancer　and　present　the　METTL5/c-Myc　axis　as　a　novel　therapeutic　strategy　for　treatment.