Abstract

An accumulating number of studies have reported that the expression levels of microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types, including renal cell carcinoma (RCC). miRNAs play essential functions in tumorigenesis and the progression of tumors by serving as oncogenes or tumor suppressors. Recently, the expression and functions of miR-138 have been studied in a number of human cancer types; however, its role in RCC remains poorly understood. In the present study, the results revealed that miR-138 was significantly downregulated in RCC cell lines and tissues, and that low expression levels of miR-138 were correlated with histological grade, tumor stage and lymph node metastasis. In functional studies, restoration of miR-138 expression inhibited cell proliferation and invasion of ACHN and A498 cells. In addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9 knockdown inhibited cell proliferation and invasion of RCC, with a similar effect to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the disease. These findings indicate that miR-138 may present a novel target for therapeutic strategies in RCC.

Highlights

  • Renal cell carcinoma (RCC) is the most common malignant cancer of the kidney in adults, accounting for almost 4% of all tumors [1]

  • MiR‐138 expression was measured in five RCC cell lines

  • Expression levels of miR‐138 were observed to be significantly lower in RCC cell lines than in HK‐2 (Fig. 1A, P

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Summary

Introduction

Renal cell carcinoma (RCC) is the most common malignant cancer of the kidney in adults, accounting for almost 4% of all tumors [1]. Clear cell RCC is the most common of these subtypes, accounting for 75 to 80% of RCC cases, and is the most aggressive [3,4,5]. It is estimated that >30% of human genes are regulated by miRNAs, and that they are involved in a variety of biological functions, including proliferation, differentiation, cell cycle, apoptosis, angiogenesis, invasion and metastasis [13,14]. An accumulating number of studies have reported that miRNA expression levels are dysregulated in a variety of human cancer types [15,16,17]. MiRNAs may be therapeutic targets for novel treatment strategies against RCC

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