H3K27ac-activated LINC00519 promotes lung squamous cell carcinoma progression by targeting miR-450b-5p/miR-515-5p/YAP1 axis

H3K27ac 激活的 LINC00519 通过靶向 miR-450b-5p/miR-515-5p/YAP1 轴促进肺鳞状细胞癌进展

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作者:Peng Ye, Xiayi Lv, Rusidanmu Aizemaiti, Jun Cheng, Pinghui Xia, Meng Di

Conclusions

H3K27ac-activated LINC00519 acts as a competing endogenous RNA (ceRNA) to promote LUSC progression by targeting miR-450b-5p/miR-515-5p/YAP1 axis.

Methods

LINC00519 expression was detected by qRT-PCR. The effect of LINC00519 on LUSC cellular activities was determined by in vitro and in vivo assays. Subcellular fractionation and FISH assays were conducted to identify the localization of LINC00519. The interaction between miR-450b-5p/miR-515-5p and LINC00519/YAP1 was verified by RIP, RNA pull-down and luciferase reporter assays.

Results

Elevated level of LINC00519 was identified in LUSC tissues and cell lines. High LINC00519 level predicted unsatisfactory prognosis. Then, loss-of-function assays suggested the inhibitive role of silenced LINC00519 in cell proliferation, migration, invasion and tumour growth and promoting effect on cell apoptosis in LUSC. Mechanically, LINC00519 was activated by H3K27 acetylation (H3K27ac). Moreover, LINC00519 sponged miR-450b-5p and miR-515-5p to up-regulate Yes1 associated transcriptional regulator (YAP1). Additionally, miR-450b-5p and miR-515-5p elicited anti-carcinogenic effects in LUSC. Finally, rescue assays validated the effect of LINC00519-miR-450b-5p-miR-515-5p-YAP1 axis in LUSC. Conclusions: H3K27ac-activated LINC00519 acts as a competing endogenous RNA (ceRNA) to promote LUSC progression by targeting miR-450b-5p/miR-515-5p/YAP1 axis.

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