Abstract
Recently, circular RNAs have been shown to function as critical regulators of many human cancers. However, the circRNA mechanism in laryngeal squamous cell carcinoma (LSCC) remains elusive. Recent investigations using bioinformatics analysis revealed high expression of hsa_circ_0023305 in LSCC tissues compared to normal tissues. Furthermore, we discovered that hsa_circ_0023305 expression level was positively correlated to tumor/node/metastasis (TNM) stage as well as lymph node metastasis in LSCC. Moreover, higher hsa_circ_0023305 levels were correlated to poorer LSCC patient outcomes. Knockdown of hsa_circ_0023305 significantly inhibited LSCC cell proliferation, invasion, and migration abilities. Our team validated that hsa_circ_0023305 functioned as a miR-218-5p sponge from a mechanistic perspective, targeting the melastatin-related transient receptor potential 7 (TRPM7) in LSCC cells. TRPM7 regulates a nonselective cation channel and promotes cancer proliferation and metastasis. Our data demonstrated that miR-218-5p was downregulated in LSCC and that miR-218-5p upregulation repressed LSCC proliferation and invasion both in vivo and in vitro. Additionally, we found that hsa_circ_0023305-mediated upregulation of TRPM7 inhibited miR-218-5p and contributed to LSCC migration, proliferation, and invasion. In summary, these data propose a new mechanism by which the hsa_circ_0023305/miR-218-5p/TRPM7 network enhances LSCC progression.
Highlights
Laryngeal cancer is a malignancy of the larynx that accounts for 1–5% of total malignant tumor incidence
The fiveyear survival rate of Laryngeal squamous cell carcinoma (LSCC) is greater than 90% with early treatment; metastasis and recurrence are the main factors that influence LSCC prognosis
RT-Quantitative Real-Time Polymerase Chain Reaction (qPCR) detection found that hsa_circ_ 0023305 expression was increased in LSCC tissues compared to adjacent tissue (Figure 1(a))
Summary
Laryngeal cancer is a malignancy of the larynx that accounts for 1–5% of total malignant tumor incidence. CircRNAs are an abundant type of endogenous RNA and have recently been rediscovered and reevaluated for their essential functions in the regulation of gene expression [5]. Emerging evidence has identified the presence of endogenous circRNAs in mammalian cells [6]. These circRNAs regulate gene expression at the posttranscriptional or transcriptional level by binding to BioMed Research International and inhibiting the function of microRNAs (miRNAs) and other molecules [6]. Our study with high-throughput sequencing identified many circRNAs with abnormal expression. Among these circRNAs, hsa_circ_0023305 expression was increased in LSCC tissues. The current study is aimed at revealing the regulatory mechanism concerning hsa_circ_ 0023305 expression in LSCC
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