lncRNA PVT1 Promotes Metastasis of Non-Small Cell Lung Cancer Through EZH2-Mediated Activation of Hippo/NOTCH1 Signaling Pathways

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Zeng Shang Gan; Xie Jian Hong; Zeng Qun Ying; Dai Shao Hua; WANG YUN; Wan Xue Mei; Liu Ji Chun

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Paper Information

Journal: Cell Journal (Yakhteh) Year:2021 | Volume:23 | Issue:1 (89) Page(s): 21-31

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Title

lncRNA PVT1 Promotes Metastasis of Non-Small Cell Lung Cancer Through EZH2-Mediated Activation of Hippo/NOTCH1 Signaling Pathways

Author(s)

Keywords

EZH2

miR-497

NSCLC

PVT1

YAP1

Abstract

Objective: Although growing evidences have showed that long non-coding RNA (lncRNAs) plasmacytoma variant translocation 1 (PVT1) 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 PVT1 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 PVT1 in NSCLC tissues and cells. The effects of PVT1 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 PVT1 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 PVT1 was up-regulated in NSCLC tissue and cell lines, promoting NSCLC cell proliferation, migration and invasion. Knockdown of PVT1 inhibited the expression of Yes-associated protein 1 (YAP1) and NOTCH1 signaling activation. Further, we have confirmed that PVT1 regulated expression of YAP1 through EZH2-mediated miR-497 promoter methylation resulting in the inhibition of miR-497 transcription and its target YAP1 upregulation, and finally NOTCH signaling pathway was activated, which promoted EMT and invasion and metastasis. Conclusions: These results suggested that lncRNA PVT1 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.

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APA: Copy

Zeng, Shang Gan, Xie, Jian Hong, Dai, Shao Hua, WANG, YUN, Wan, Xue Mei, Liu, Ji Chun, & Zeng, Qun Ying. (2021). lncRNA PVT1 Promotes Metastasis of Non-Small Cell Lung Cancer Through EZH2-Mediated Activation of Hippo/NOTCH1 Signaling Pathways. CELL JOURNAL (YAKHTEH), 23(1 (89)), 21-31. SID. https://sid.ir/paper/768916/en

Vancouver: Copy

Zeng Shang Gan, Xie Jian Hong, Dai Shao Hua, WANG YUN, Wan Xue Mei, Liu Ji Chun, Zeng Qun Ying. lncRNA PVT1 Promotes Metastasis of Non-Small Cell Lung Cancer Through EZH2-Mediated Activation of Hippo/NOTCH1 Signaling Pathways. CELL JOURNAL (YAKHTEH)[Internet]. 2021;23(1 (89)):21-31. Available from: https://sid.ir/paper/768916/en

IEEE: Copy

Shang Gan Zeng, Jian Hong Xie, Shao Hua Dai, YUN WANG, Xue Mei Wan, Ji Chun Liu, and Qun Ying Zeng, “lncRNA PVT1 Promotes Metastasis of Non-Small Cell Lung Cancer Through EZH2-Mediated Activation of Hippo/NOTCH1 Signaling Pathways,” CELL JOURNAL (YAKHTEH), vol. 23, no. 1 (89), pp. 21–31, 2021, [Online]. Available: https://sid.ir/paper/768916/en

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