Abstract
Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer. The regulation of LSCC progression by long non-coding RNA (lncRNA) was not well understood. In this study, we reported that the lncRNA H19 was upregulated in LSCC. The expression levels of H19 were inversely correlated with the survival rate of LSCC patients. Knockdown of H19 expression inhibited LSCC cell migration, invasion and proliferation. We identified microRNA miR-148a-3p as an inhibitory target for H19. Overexpression of miR-148a-3p reduced LSCC migration, invasion and proliferation cell, while inhibition of miR-148a-3p did the opposite. The inhibition of LSCC progression induced by H19 knockdown required the activity of miR-148a-3p. We also identified DNA methyltransferase enzyme DNMT1 as a target of miR-148a-3p. Cellular DNA methylation levels were inhibited by both miR-148a-3p overexpression and H19 knockdown. In summary, our study demonstrated that the lncRNA H19 promoted LSCC progression via miR-148a-3p and DNMT1.
Highlights
Head and neck squamous cell carcinoma is the sixth most common cancer in the world, among which the laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignancy [1]
We found that the long non-coding RNA (lncRNA) H19 was upregulated in LSCC and that the expression levels of H19 were inversely correlated with the survival rate of LSCC patients
Our study demonstrated that the lncRNA H19 could promote LSCC progression via miR-148a-3p and DNMT1, and that DNA methylation was involved in the regulatory mechanism
Summary
Head and neck squamous cell carcinoma is the sixth most common cancer in the world, among which the laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignancy [1]. Encouraging progress in the diagnosis and treatment for LSCC has been achieved in the past 20 years, the overall survival rate remains unfavorable. A recent study has shown that the overall 1-and 2-year survival rates for LSCC patients without treatment are only 56.4% and 26.5%, respectively [2]. Small ncRNAs have been shown to act primarily as negative regulators of gene expression. A number of microRNAs, which belong to the small ncRNA family, have been demonstrated to function as oncogenes or tumor suppressor genes for LSCC in our previous studies [4,5,6,7,8]. Long ncRNAs (lncRNAs) are poorly conserved among species [9, 10], but accumulating evidences indicate that lncRNAs could play important roles in a variety of biological processes and may well be involved in the development of cancer and other human diseases [11, 12]
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