L3MBTL2　is　a　crucial　component　of　ncPRC1.6　and　has　been　implicated　in　transcriptional　repression　and　chromatin　compaction.　However,　the　repression　mechanism　of　L3MBTL2　and　its　biological　functions　are　largely　undefined.　Here,　we　found　that　L3MBTL2　plays　a　distinct　oncogenic　role　in　tumor　development.　We　demonstrated　that　L3MBTL2　repressed　downstream　CGA　through　an　H2AK119ub1-dependent　mechanism.　Importantly,　the　binding　of　the　MGA/　MAX　heterodimer　to　the　E-box　on　the　CGA　promoter　enhanced　the　specific　selective　repression　of　CGA　by　L3MBTL2.　CGA　encodes　the　alpha　subunit　of　glycoprotein　hormones;　however,　we　showed　that　CGA　plays　an　individual　tumor　suppressor　role　in　PDAC.　Moreover,　CGA-transcript1　(T1)　was　identified　as　the　major　transcript,　and　the　tumor　suppression　function　of　CGA-T1　depends　on　its　own　glycosylation.　Furthermore,　glycosylated　CGA-T1　inhibited　PDAC,　partly　by　repression　of　autophagy　through　multiple　pathways,　including　PI3K/Akt/mTOR　and　TP53INP2　pathways.　These　findings　reveal　the　important　roles　of　L3MBTL2　and　CGA　in　tumor　development.