Abstract
MicroRNA (miR)-338-3p has been reported to be involved in tumor progression and development in various types of cancer. However, the biological function of miR-338-3p and its related molecular pathways involved in the progression of renal cell carcinoma (RCC) are unknown. The present study aimed to investigate the biological role and underlying mechanism of miR-338-3p in RCC cells. It was demonstrated that miR-338-3p expression level was significantly downregulated (P<0.05) in RCC tissues and cell lines. Clinical association analysis indicated that low expression of miR-338-3p was significantly associated with advanced TNM stage and lymph node metastasis (P<0.05). Function assays revealed that restoration of miR-338-3p in RCC cells significantly inhibited cell proliferation, colony formation, migration and invasion (P<0.05). Notably, sex-determining region Y-box 4 (SOX4) was identified as a direct target of miR-338-3p in RCC cells through a luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Furthermore, SOX4 overexpression partially rescued miR-338-3p-mediated inhibition of cell proliferation, colony formation, migration and invasion in RCC cells. These results suggested that miR-338-3p functioned as a tumor suppressor in RCC cells by modulating SOX4, suggesting that miR-338-3p may have a potential use in the treatment of RCC.
Highlights
Renal cell carcinoma (RCC), accounting for 2‐3% of all tumor malignancies in humans, is the most lethal urologic tumor [1]
It was demonstrated that the expression of miR‐338‐3p in the RCC cell lines, 786‐O, ACHN, Caki‐1 and Caki‐2, was significantly lower than that observed in the human renal proximal tubule epithelial cell line, HK‐2 (P
Cell line 786‐O, which had the highest expression of miR‐338‐3p of the four RCC cell lines, and Caki‐1, which had the lowest expression of miR‐338‐3p of the four cell lines, were selected as representatives to perform subsequent experiments
Summary
Renal cell carcinoma (RCC), accounting for 2‐3% of all tumor malignancies in humans, is the most lethal urologic tumor [1]. MicroRNA (miR) are a class of short, single stranded, non‐coding RNA molecules, of 19‐25 nucleotides in length, that act as important regulators of gene expression by binding to the 3'‐untranslated region (UTR) of specific target mRNA [4]. Study has demonstrated that miR are involved in various biological processes, such as cell growth, migration, invasion, apoptosis, metabolism and cellular differentiation [5,6]. Accumulating evidence suggests that miR could have oncogenic or tumor‐suppressive roles in the regulation of cell growth, migration and invasion by repressing their target genes [7,8]. Some miR have been reported to be involved in RCC procession, and may serve as diagnostic markers or therapy agents for RCC [9,10]
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