Abstract
The aim of the present study is to investigate the role of microRNA (miRNA/miR)-409-3p in the proliferation, invasion and migration of tongue squamous cell carcinoma (TSCC) cells via targeting radixin (RDX) gene. The expression of miR-409-3p was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in TSCC tissue and cell lines. The binding of miR-409-3p to RDX was investigated by performing a dual-luciferase reporter gene assay. Tca8113 cells were selected to transfect with miR-409-3p mimic/inhibitor, small interfering (si)-RDX, and miR-409-3p inhibitor + si-RDX, as well as negative control (NC) respectively. The proliferative, migratory and invasive abilities of transfected Tca8113 cells were investigated by cell-counting-kit-8, wound-healing and Transwell assays, respectively. Additionally, a tumor xenograft model was constructed to examine the effects of miR-409-3p on the tumor growth and lymphatic metastasis in nude mice. A significant downregulation was detected in miR-409-3p expression in TSCC tissues and cells (all P<0.05) compared with normal tongue mucosa tissues and cell line, which was associated with lymph node metastasis and tumor-node metastasis staging (both P<0.05). The results from the dual-luciferase reporter gene assay indicated that RDX is a potential target gene of miR-409-3p. Compared with the blank group, a marked reduction in RDX expression, cell proliferation, migration and invasion was detected in the miR-409-3p mimic group and si-RDX group (all P<0.05). Conversely, the reverse was observed in cells that were transfected with the miR-409-3p inhibitor. Furthermore, si-RDX is able to reverse the effect of miR-409-3p inhibitor on cell proliferation, invasion and migration (all P<0.05). The results form the tumor xenograft model of nude mice verified that miR-409-3p mimic is able to inhibit the growth of Tca8113 tumor cells and lymph node metastasis in nude mice. miR-409-3p may delay the proliferation of TSCC cells by inhibiting of RDX so as to decrease its migratory and invasive abilities. Therefore, miR-409-3p may be a potential target for the clinical treatment of TSCC.
Highlights
As the most common malignancy of head and neck, oral squamous cell carcinoma (OSCC) ranks the top six of malignant tumors worldwide with unsatisfactory prognosis [1]
Compared with the human oral keratinocytes (HOK) cells, the expression of miR‐409‐3p was significantly decreased in Tongue squamous cell carcinoma (TSCC) cell lines (Tca8113, SCC9, SCC25 and Ca127; all P
A significant association between miR‐409‐3p expression and lymph node metastasis and tumor‐node metastasis (TNM) stage was presented in Table II. miR‐409‐3p expression was lower in patients with TSCC and lymph node metastasis and advanced TNM stages compared with those with no lymph node metastasis and with low TNM stages (Table II)
Summary
As the most common malignancy of head and neck, oral squamous cell carcinoma (OSCC) ranks the top six of malignant tumors worldwide with unsatisfactory prognosis [1]. Despite of surgery combined with chemoradiotherapy as the primary treatment for TSCC, postoperative recurrence and the rate of distant metastasis remain high and the total 5‐year survival rate is only ~50~60%. Josson et al [15] identified elevated miR‐409‐3p/‐5p levels in prostate cancer, thereby indicating that it may facilitate tumorigenesis, CHEN and DAI: miR-409-3p TARGETS RDX IN TSCC epithelial‐to‐mesenchymal transition, as well as bone metastasis of prostate cancer. This suggests that miR‐409‐3p may serve important functions in different tumor progression, including TSCC
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