lncRNA Promotes Pancreatic Ductal Adenocarcinoma Growth and Leads to a Poor Clinical Outcome via Sponging miR-484 and Interacting with YAP.

Purpose: Long noncoding RNAs (lncRNA) have been observed in various cancer types. Our bioinformatic analysis of existing databases demonstrated overexpression of lncRNA in pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the roles and mechanisms of in PDAC.

Experimental Design: The overexpression of in samples of patients with pancreatic cancer was characterized and was associated with clinical outcomes. The nonprotein coding property of the was verified. Various and experiments were performed to investigate the interaction between and YAP signaling.

Results: We demonstrated that lncRNA is overexpressed in PDAC in multiple patient sample sets, which is significantly associated with poor outcome of patients with PDAC. promotes PDAC cells growth both and . exerts its effects via enhancing YAP signaling. Ectopic YAP expression overcame the effects of knockdown. Inversely, YAP knockdown diminished the effects of overexpression. acts as a competing endogenous RNA for miR-484, leading to YAP upregulation. Moreover, binds to YAP protein and inhibits the phosphorylation-mediated inactivation of YAP by LATS1. Reciprocally, YAP/TEAD1 complex promotes transcription to form a feed-forward circuit. Importantly, level positively correlates with YAP expression in PDAC tissues. YAP overexpression also predicts a poor outcome in patients with PDAC.

Conclusions: Our findings indicate that plays an important role in PDAC growth via enhancing YAP signaling, which in turn also modulates transcription. /YAP axis may serve as a potential biomarker and therapeutic target for PDAC treatment.