Abstract
Our previous study revealed that the miR-199 family (miR-199a-5p/-3p and miR-199b-5p/-3p) acts as tumor-suppressive miRNAs in head and neck squamous cell carcinoma (HNSCC). Furthermore, recent studies have indicated that the passenger strands of miRNAs are involved in cancer pathogenesis. The aim of this study was to identify cancer-promoting genes commonly regulated by miR-199-5p and miR-199-3p in HNSCC cells. Our in silico analysis and luciferase reporter assay identified paxillin (PXN) as a direct target of both miR-199-5p and miR-199-3p in HNSCC cells. Analysis of the cancer genome atlas (TCGA) database showed that expression of PXN significantly predicted a worse prognosis (5-year overall survival rate; p = 0.0283). PXN expression was identified as an independent factor predicting patient survival according to multivariate Cox regression analyses (p = 0.0452). Overexpression of PXN was detected in HNSCC clinical specimens by immunostaining. Functional assays in HNSCC cells showed that knockdown of PXN expression attenuated cancer cell migration and invasion, suggesting that aberrant expression of PXN contributed to HNSCC cell aggressiveness. Our miRNA-based approach will provide new insights into the molecular pathogenesis of HNSCC.
Highlights
Global cancer statistics in 2018 stated that head and neck squamous cell carcinoma (HNSCC) was the eighth most common human malignancy worldwide [1]
Of PXN, but not with a vector lacking the miR-199-3p-binding site in the PXN 30 untranslated region (UTR). These findings suggest that miR-199-5p and miR-199-3p bind directly to the 30 UTR of PXN and regulate the expression of PXN in HNSCC cells
Our functional assays showed that these passenger strands contribute to HNSCC oncogenesis, and that several of their target genes are closely associated with HNSCC pathogenesis [17,24,26,27]
Summary
Global cancer statistics in 2018 stated that head and neck squamous cell carcinoma (HNSCC) was the eighth most common human malignancy worldwide [1]. There are approximately more than 800,000 new HNSCC cases diagnosed and 430,000 deaths from HNSCC [2]. HNSCC arises from the oral cavity, hypopharynx, nasopharynx, and larynx, and the most common subtype of HNSCC is oral squamous cell carcinoma (OSCC) [3]. 60% of patients with HNSCC are at an advanced stage at the time of diagnosis [6]. Aggressive progression of HNSCC is characterized by high rates of recurrence, distant metastasis, and drug resistance acquired by cancer cells during treatment [7]. The treatment outcomes of HNSCC have not improved significantly in recent decades, and the molecular mechanisms of malignant transformation of HNSCC are not completely understood
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