Accumulating　evidence　suggests　that　cancer-associated　mesenchymal　stem　cells　(MSC)　contribute　to　the　development　and　metastasis　of　hepatocellular　carcinoma　(HCC).　Aberrant　expression　of　long　noncoding　RNAs　(lncRNA)　has　been　associated　with　these　processes　but　cellular　mechanisms　are　obscure.　In　this　study,　we　report　that　HCC-associated　mesenchymal　stem　cells　(HCC-MSC)　promote　epithelial-mesenchymal　transition　(EMT)　and　liver　tumorigenesis.　We　identified　a　novel　lncRNA　that　we　termed　lncRNA-MUF　(MSC-upregulated　factor)　that　is　highly　expressed　in　HCC　tissues　and　correlated　with　poor　prognosis.　Depleting　lncRNA-MUF　in　HCC　cells　repressed　EMT　and　inhibited　their　tumorigenic　potential.　Conversely,　lncRNA-MUF　overexpression　accelerated　EMT　and　malignant　capacity.　Mechanistic　investigations　showed　that　lncRNA-MUF　bound　Annexin　A2　(ANXA2)　and　activated　Wnt/beta-catenin　signaling　and　EMT.　Furthermore,　lncRNA-MUF　acted　as　a　competing　endogenous　RNA　for　miR-34a,　leading　to　Snail1　upregulation　and　EMT　activation.　Collectively,　our　findings　establish　a　lncRNA-mediated　process　in　MSC　that　facilitates　hepatocarcinogenesis,　with　potential　implications　for　therapeutic　targeting.　(C)　2017　AACR.