Hsa_circ_0000825 Promotes the Progression of Laryngeal Squamous Cell Carcinoma by Sponging MiR-766 and Interacting with ELAVL1

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Sep 25

PMID 39319166

Authors

Miaomiao Yu

Huan Cao

Jianwang Yang

Tao Liu

Baoshan Wang

Affiliations

Soon will be listed here.

Abstract

Emerging evidence suggests that circular RNAs (circRNAs) are involved in the regulation of tumourigenesis and progression of a variety of malignant tumours. In this study, we aimed to identify laryngeal squamous cell carcinoma (LSCC)-specific circRNAs and explore their biological functions and underlying molecular mechanisms. Employing microarray and qRT-PCR, hsa_circ_0000825 was found to be significantly increased in LSCC tissues versus para-cancerous tissues. High hsa_circ_0000825 expression was positively associated with advanced clinical stages, lymph node metastasis, and poor survival. Furthermore, the overexpression of hsa_circ_0000825 in TU177 and AMC-HN-8 cells promoted cell proliferation. Transwell assays showed enhanced migration and invasion of TU177 and AMC-HN-8 cells upon overexpression of hsa_circ_0000825. Conversely, the knockdown of hsa_circ_0000825 had the opposite effect. Xenograft tumours in BALB/c nude mice derived from hsa_circ_0000825-overexpressed TU177 cells showed greater volume and weight than those derived from control TU177 cells. Mechanistically, nuclear-cytoplasmic fractionation assay confirmed that hsa_circ_0000825 was mainly located in the cytoplasm of TU177 and AMC-HN-8 cells. The AGO2-RNA immunoprecipitation (RIP) assay revealed that hsa_circ_0000825 was significantly enriched in the AGO2-precipitated complex in both TU177 and AMC-HN-8 cells, suggesting that this circRNA may function via a competitive endogenous RNA (ceRNA) mechanism. Next, bioinformatics analysis, biotinylated-oligo pull-down assay and dual-luciferase reporter assay verified that miR-766 could be sponged by hsa_circ_0000825 and also target 3'UTR of HOXD10 mRNA. Moreover, miR-766 was shown to be involved in the pro-oncogenic effect of hsa_circ_0000825. This occurred via the mediation of hsa_circ_0000825-enhanced HOXD10 mRNA by the ceRNA mechanism in TU177 and AMC-HN-8 cells. Besides, RNA-binding protein (RBP) ELAVL1 interacted with hsa_circ_0000825 in TU177 and AMC-HN-8 cells, as revealed through bioinformatics analysis, biotinylated-oligo pull-down assays, and RIP assays. ELAVL1 knockdown decreased cell proliferation by 38 % and 34 % in hsa_circ_0000825-overexpressed TU177 and AMC-HN-8 cells ( < 0.05). Similarly, ELAVL1 was involved in the pro-migration and pro-invasion effects of hsa_circ_0000825 overexpression. In addition, comprehensive analysis of mRNA-seq in hsa_circ_0000825-overexpressed TU177 cells, as well as catRAPID and TCGA databases, suggested that ITGB2, HOXD10, and MTCL1 might be crucial downstream target mRNAs of ELAVL1 in LSCC, participating in the hsa_circ_0000825-ELAVL1 axis pro-oncogenic effect. Taken together, hsa_circ_0000825 plays a pro-oncogenic role in LSCC via the miR-766/HOXD10 axis and ELAVL1 and may serve as a promising specific biomarker and therapeutic target for LSCC.

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