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

Abstract

Objectives Long non‐coding RNAs (lncRNAs) are extensively reported as participants in the biological process of diverse malignancies, including lung squamous cell carcinoma (LUSC). Long intergenic non‐protein coding RNA 519 (LINC00519) is identified as a novel lncRNA which has not yet been studied in cancers. Materials and 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.

<p>Long Intergenic Non-Protein Coding RNA 519 Promotes the Biological Activities of Tongue Squamous Cell Carcinoma by Sponging microRNA-876-3p and Consequently Upregulating MACC1</p>

“…LINC00519 expression is upregulated in lung squamous cell carcinoma. 26 High LINC00519 expression is closely associated with an unsatisfactory prognosis in patients with lung squamous cell carcinoma. 26 Functionally, LINC00519 exerts pro-oncogenic roles in lung squamous cell carcinoma cells.…”

“…26 High LINC00519 expression is closely associated with an unsatisfactory prognosis in patients with lung squamous cell carcinoma. 26 Functionally, LINC00519 exerts pro-oncogenic roles in lung squamous cell carcinoma cells. 26 In contrast, the expression profile and biological functions of LINC00519 in TSCC have rarely been documented.…”

“…26 Functionally, LINC00519 exerts pro-oncogenic roles in lung squamous cell carcinoma cells. 26 In contrast, the expression profile and biological functions of LINC00519 in TSCC have rarely been documented. In this study, LINC00519 was highly expressed in TSCC from both the TCGA database and our own database.…”

“…Long intergenic non-protein coding RNA 519 (LINC00519) was previously confirmed to promote the development of lung squamous cell carcinoma. 26 Nevertheless, the expression and roles of LINC00519 in TSCC and the related mechanisms have not been well studied. Therefore, we detected the expression of LINC00519 in TSCC and examined its clinical significance.…”

Long Intergenic Non-Coding RNAs in HNSCC: From “Junk DNA” to Important Prognostic Factor

“…Long intergenic non-protein-coding RNA 519 (LINC00519) was first described in lung squamous cell carcinoma (LUSC) as an oncogene [96]. Localization analysis indicated that the vast majority of these lincRNA molecules can be found in the cytoplasm where they act as an miRNA-sequestering sponge [97].…”