Abstract
BackgroundmiR-34a is an important tumor suppressor gene in various cancer types. But little is known about the dysregulation of miR-34a in tongue squamous cell carcinoma (TSCC). In this study, we investigate the expression and potential role of miR-34a in TSCC.MethodsWe evaluated miR-34a expression and its relationship with clinicopathological characters in 75 pairs of TSCC samples, and confirmed the role of miR-34a for predicting lymph node metastases from a further 15 pairs of paraffin-embedded TSCC specimens with stringent clinicopathological recruitment criteria using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of miR-34a on cell proliferation, migration and invasion were examined in TSCC cell lines using Cell Counting Kit-8 assay, wound healing assay and transwell assay, respectively. The effects of miR-34a on the expression of matrix metalloproteinase (MMP) 9 and 14 were detected by luciferase reporter assays and Western blot analysis. The expression of miR-34a, MMP9 and MMP14 were also confirmed in TSCC samples by in situ hybridization and immunohistochemistry.ResultsmiR-34a expression in tumor tissues from TSCC patients with positive lymph node metastases was significantly lower than that with negative lymph node metastases. Overexpression of miR-34a significantly suppressed migration and invasion in TSCC cells and simultaneously inhibited the expression of MMP9 and MMP14 through targeting the coding region and the 3′untranslated region, respectively. Moreover, miR-34a expression in TSCC was inversely correlated with protein expression of MMP9 and MMP14 in the TSCC samples.ConclusionsmiR-34a plays an important role in lymph node metastases of TSCC through targeting MMP9 and MMP14 and may have potential applications in prognosis prediction and gene therapy for lymph node metastases of TSCC patients.
Highlights
Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is characterized by its high rate of proliferation and lymph nodal metastases [1,2]
The results showed that only MMP9 (GenBank accession number, NM_004994.2) and MMP14 (GenBank accession number, NM_004995.3) messenger RNAs (mRNAs) contain putative miR-34a target sites
We further analyzed the expression levels of miR-34a from formalin-fixed paraffin-embedded (FFPE) tissues including a group of 15 tongue squamous cell carcinoma (TSCC) patients with negative lymph node metastases (‘‘fortunate group’’) compared with another group of 15 TSCC patients with positive lymph node metastases (‘‘unfortunate group’’) matched for age, gender, location of the primary carcinoma, pathologic differentiation, TNM stage, and treatment modality (Table S2)
Summary
Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is characterized by its high rate of proliferation and lymph nodal metastases [1,2]. The presence of cervical lymph node metastases is one of the most important prognostic factors for patients with TSCC [3,4]. If cervical lymph node metastases of TSCC are apparent at presentation of patients, neck dissection is necessary. The treatment of early-stage TSCC patients with clinically negative cervical lymph node is still controversial [5]. Clinicopathological characteristics often guide the clinician’s treatment choices, biomarkers of cervical lymph node metastases in TSCC would greatly assist the decision-making for appropriate clinical treatment [6]. We investigate the expression and potential role of miR-34a in TSCC
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