The Biological Role of Mir-145-3p in Head and Neck Squamous Cell Carcinoma
Introduction. Head and neck cancer is the sixth leading cancer worldwide (1,2). Anatomical complexity of the organs in the head and neck region make it difficult in treating the disease, resulting in high recurrence rates and poor prognosis (1,2). These issues promoted the research of potential non-invasive treatment/prognostic options such as microRNAs (miR). MiRs are small, non-coding RNA molecules composed of two strands: the guide and passenger strands (3,4). The guide strand is involved in multiple cell processes such as differentiation and proliferation, while the passenger strand is usually degraded (3,4). MiRs have been shown to be associated with several types of cancers through dis-regulation and up-regulation of several genes at the transcriptional level (2-5). One of the most heavily researched miRs is miR-145, which has been associated as a tumor suppressor in several cancers including head and neck Squamous Cell Carcinoma (HNSCC) (3,5). Although research has shown that miR-145 is significantly down-regulated in HNSCC and other cancers (3), the mechanisms and prognostic/therapeutic potential of the passenger strand of miR-145 is still unclear. Methods. 22 HNSCC samples were collected using SAS and HSC3 cell lines for transfection. Cell proliferation, migration and invasion were studied using specific assays. Biological activity of miR-145-5p (guide strand) and miR-145-3p (passenger strand) was tested using Ago2 immunoprecipitation. Putative genes targets of miR-145-3p were identified using in-silico and genome-wide analyses. The relevance of the gene targets in patient survival rates was assessed using The Cancer Genome Atlas. Pathways regulated by MYO1B were analyzed using si-MYO1B-transfected SAS cells and microarray analysis. Results. MiRNA-145-5p and miR-145-3p expression levels were significantly reduced in SAS and HSC3 cell lines (p < 0.0001) (3). Cell proliferation, migration and invasion were significantly reduced in miRNA-145-5p and miRNA-145-3p transfectants (3). Both strands of miRNA-145 showed significant biological activity in transfected cell lines (p < 0.0001) (3). A total of 3,164 genes were predicted as targets of miRNA-145-3p, out of which 14 genes were upregulated in HNSCC being associated with poor prognosis, including MYO1B (3). MiiRNA-145-3p was negatively correlated with MYO1B expression in transfectants (p=0.0025, Spearman’s R=-0.461) (3). Conclusions. MiR-145-5p and miR-145-3p are significantly down-regulated in HNSCC cell lines. MiR-145-3p showed significant biological activity by decreased cell proliferation, migration and invasion by knockdown of MYO1B gene expression. Other genes associated with poor prognosis are targeted by miR-145-3p, resulting in antitumor functions similar to miR145-5p in HNSCC cells. Further analyses of the pathways mediated by miR145-3p could contribute to novel treatments and diagnostic tools for HNSCC.
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