Regulation of ITGA3 by the anti‐tumor miR‐199 family inhibits cancer cell migration and invasion in head and neck cancer

Abstract

For patients with head and neck squamous cell carcinoma (HNSCC), survival rates have not improved due to local recurrence and distant metastasis. Current targeted molecular therapies do not substantially benefit HNSCC patients. Therefore, it is necessary to use advanced genomic approaches to elucidate the molecular mechanisms underlying the aggressiveness of HNSCC cells. Analysis of our microRNA (miRNA) expression signature by RNA sequencing showed that the miR‐199 family (miR‐199a‐5p, miR‐199a‐3p, miR‐199b‐5p and miR‐199b‐3p) was significantly reduced in cancer tissues. Ectopic expression of mature miRNA demonstrated that all members of the miR‐199 family inhibited cancer cell migration and invasion by HNSCC cell lines (SAS and HSC3). These findings suggested that both passenger strands and guide strands of miRNA are involved in cancer pathogenesis. In silico database and genome‐wide gene expression analyses revealed that the gene coding for integrin α3 (ITGA3) was regulated by all members of the miR‐199 family in HNSCC cells. Knockdown of ITGA3 significantly inhibited cancer cell migration and invasion by HNSCC cells. Moreover, overexpression of ITGA3 was confirmed in HNSCC specimens, and high expression of ITGA3 predicted poorer survival of the patients (P = 0.0048). Our data revealed that both strands of pre‐miR‐199a (miR‐199a‐5p and miR‐199a‐3p) and pre‐miR‐199b (miR‐199b‐5p and miR‐199b‐3p) acted as anti‐tumor miRNA in HNSCC cells. Importantly, the involvement of passenger strand miRNA in the regulation of cellular processes is a novel concept in RNA research. Novel miRNA‐based approaches for HNSCC can be used to identify potential targets for the development of new therapeutic strategies.

Molecular pathogenesis of renal cell carcinoma: Impact of the anti‐tumor miR‐29 family on gene regulation

“…Previous reports showed that overexpression of SERPINH1 promotes procollagen production, resulting in the development of the epithelial mesenchymal transition . Recent studies suggested that aberrantly expressed ECM genes and their receptors enhanced cancer cell aggressiveness . Elucidation of genes modulated by SERPINH1 might provide novel therapeutic approaches in RCC.…”

Involvement of dual‐strand of the miR‐144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma

“…After a 48‐hour incubation period, miRNAs were isolated by immunoprecipitation using a microRNA Isolation Kit for Human Ago2 (Wako, Osaka, Japan). We then assessed the expression of Ago2‐conjugated miRNAs by qRT‐PCR, as described in previous studies …”

“…The clinical significance of miRNAs and their target genes in LUSQ was investigated with TCGA database (https://tcga-data.nci.nih.gov/tcga/). The gene expression and clinical data were retrieved from cBioPortal (http://www.cbioportal.org/) and OncoLnc (http://www.oncolnc.org) (data downloaded on April 28, 2018) …”

Micro‐ribonucleic acid expression signature of metastatic castration‐resistant prostate cancer: Regulation of NCAPH by antitumor miR‐199a/b‐3p

“…In the search miRNA database (miRBase: http://www.mirbase.org/), the expression of miR‐199a/b‐3p annotated as passenger strands is higher than that of miR‐199a/b‐5p . Our previous study also showed that the expression level of miR‐199a/b‐3p in head and neck cancer was more abundant than miR‐199a/b‐5p . These facts might indicate characteristics of the miR‐199 family, suggesting that the passenger strand could exert more function in the cell in the miR‐199 family.…”

“…The miR‐199 family members reportedly act as tumor suppressors in several cancers. Recently, we showed that all members of the miR‐199 family acted as antitumor miRNAs through their targeting of integrin‐mediated oncogenic signaling in head and neck squamous cell carcinoma . In PCa, downregulation of miR‐199a‐5p and miR‐199b‐5p induced HIF‐1α expression, and these events enhanced PCa development .…”