lncRNA Promotes Metastasis of Non-Small Cell Lung Cancer Through EZH2-Mediated Activation of Hippo/NOTCH1 Signaling Pathways.

Objective: Although growing evidences have showed that long non-coding RNA (lncRNAs) plasmacytoma variant translocation 1 () plays a critical role in the progression of non-small cell lung cancer (NSCLC), there are still many unsolved mysteries remains to be deeply elucidated. This study aimed to find a new underlying mechanism of in regulating the tumorigenesis and development of NSCLC.

Materials And Methods: In this experimental study, Quantitative reverse transcription polymerase chain reaction (qRTPCR) was used to profile the expression of in NSCLC tissues and cells. The effects of on cell growth, migration and invasion were detected by colony formation assay, Matrigel-free transwell and Matrigel transwell assays, respectively. Changes of the key protein expression in Hippo and NOTCH signaling pathways, as well as epithelialmesenchymal transition (EMT) markers, were analyzed using western blot. Interaction of with enhancer of zeste homolog 2 (EZH2) was verified by RNA pull-down, and their binding to the downstream targets was detected by Chromatin Immunoprecipitation (ChIP) assays.

Results: These results showed that was up-regulated in NSCLC tissue and cell lines, promoting NSCLC cell proliferation, migration and invasion. Knockdown of inhibited the expression of Yes-associated protein 1 (YAP1) and NOTCH1 signaling activation. Further, we have confirmed that regulated expression of YAP1 through EZH2-mediated promoter methylation resulting in the inhibition of transcription and its target YAP1 upregulation, and finally NOTCH signaling pathway was activated, which promoted EMT and invasion and metastasis.

Conclusion: These results suggested that lncRNA promotes NSCLC metastasis through EZH2-mediated activation of Hippo/NOTCH1 signaling pathways. This study provides a new opportunity to advance our understanding in the potential mechanism of NSCLC development.