miR-144-3p, a tumor suppressive microRNA targeting ETS-1 in laryngeal squamous cell carcinoma

Abstract

Regional lymph node metastasis and distant metastasis are critical in the prognosis of laryngeal squamous cell carcinoma (LSCC). This study investigated the roles of miR-144-3p and E26 transformation specific-1 (ETS-1) in the invasion and migration of LSCC cells. The effects of miR-144-3p and ETS-1 on FaDu and Hep2 cell growth, migration and invasion were determined. Suppression of ETS-1 by miR-144-3p was confirmed using luciferase assays; the effects of ETS-1 silencing were determined using a xenograft tumor model. The expression of ETS-1 was analyzed in 71 paraffin-embedded tissue biopsies and eight fresh frozen biopsies obtained from LSCC patients. miR-144-3p inhibited the growth, invasion and migration of FaDu and Hep2 cells in part through suppression of epithelial-mesenchymal transition as determined by increased E-cadherin and α-catenin and reduced fibronectin and vimentin expression. Additionally, ETS-1 is a molecular target of miR-144-3p, and silencing ETS-1 expression inhibited FaDu and Hep2 cell invasion and migration as well as reduced Hep2 xenograft tumor volume. In LSCC, the expression of ETS-1 is upregulated with disease progression, and higher ETS-1 expression, which was negatively associated with miR-144-3p levels, adversely corresponded with prognoses. Thus, upregulated ETS-1 levels may promote LSCC metastasis, resulting in poor patient prognosis.

miR-144 inhibits growth and metastasis of cervical cancer cells by targeting VEGFA and VEGFC

“…Hence, identification of miRNAs and their target genes involved in tumorigenesis will provide key clues for the development of novel diagnostic tools and therapies for patients with cervical cancer. miR-144 is located on chromosome 17q11.2 of the human genome, which has been reported to be downregulated in esophageal squamous cell cancer (28), laryngeal squamous cell carcinoma (29), lung cancer (30) and bladder cancer (31). The present study assessed the expression levels of miR-144 in cervical cancer tissues and their matched normal cervical tissues to determine the effects of miR-144 on the malignant progression of cervical cancer.…”

“…Matsushita et al (34) suggested that tumor-suppressive miR-144 directly targeted the transcripts of CCNE1/2 as potential prognostic biomarkers in bladder cancer. Zhang et al (30) reported that miR-144-3p, a tumor suppressive miRNA, targeted ETS-1 in laryngeal squamous cell carcinoma. The present study expanded the current knowledge regarding the role of miR-144 in cervical cancer and suggested a tumor suppressive role via inhibition of cellular growth, migration and invasion.…”

Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance

“…Our data showed that both strands of miR‐144‐5p and miR‐144‐3p had antitumor functions in RCC cells. Many studies have reported that miR‐144‐3p acted as an antitumor miRNA in several types of cancers . In contrast to recent analyses of miR‐144‐3p , few papers have examined the function of miR‐144‐5p in cancer cells.…”

A genetic view of laryngeal cancer heterogeneity

“…75,76 It has been considered that miRs regulate around 60% of genes in the numan genome. The analysis of miR expression variation in Laryngeal cancer by a variety of techniques including broadly used miR microarrays and massive sequencing have shown a large variety of miRs deregulated in laryngeal cancer, many of them with diagnosis or prognosis value (reviewed in 77 ) 78,79 (Table 1). These miRs behave as oncogenes (oncomirs) or tumor suppressorS in laryngeal cancer according the effect of the target.…”