Abstract

Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of clear cell renal cell carcinoma (ccRCC) through their participation in a number of critical biological processes. Therefore, an in‑depth investigation into miRNAs and their biological roles within ccRCC may provide useful insights and lead to the identification of novel therapeutic methods for patients with ccRCC. miRNA‑599 (miR‑599) serves critical roles in different types of human cancer. However, the expression pattern, biological function and molecular mechanism of miR‑599 in ccRCC remain unknown. The present study aimed to detect the expression level of miR‑599 in ccRCC, examine its effect on ccRCC progression and further explore the possible underlying mechanisms. It was observed that miR‑599 was significantly underexpressed in ccRCC tissues and cell lines compared with the control. Functional assays revealed that restored expression of miR‑599 restricted the proliferation and invasion of ccRCC cells. Bioinformatics analysis, luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis demonstrated that high‑mobility group AT‑hook 2 (HMGA2) was a direct target of miR‑599 in ccRCC. HMGA2 knockdown simulated the suppressive effects caused by miR‑599 overexpression in ccRCC. Recovered HMGA2 expression partially rescued the miR‑599‑mediated inhibition of ccRCC proliferation and invasion. These results suggest that miR‑599 may serve tumour suppressive roles in ccRCC by directly targeting HMGA2, indicating that miR‑599 may have potential as a treatment for patients with ccRCC.

Highlights

  • Renal cell carcinoma (RCC) is a common human urologic cancer that accounts for approximately 3% of all malignancies [1]

  • MiR‐599 expression level decreased in the A498 and 786‐O cell lines compared with HK‐2 (P

  • Dysregulation of miRNAs is involved in the occurrence and development of ccRCC through their participation in many important biological processes, such as cell proliferation, cycle, apoptosis, angiogenesis, migration, invasion and metastasis [29,30,31]

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Summary

Introduction

Renal cell carcinoma (RCC) is a common human urologic cancer that accounts for approximately 3% of all malignancies [1]. RCC can be histologically classified into four subtypes, namely, clear cell RCC (ccRCC), papillary RCC, chromophobe RCC and oncocytoma [3]. CcRCC, the most common subtype of RCC, accounts for 70‐80% of RCC cases [4]. Despite considerable advancements in cancer diagnosis and therapy, the curative effects on patients at advanced stages remain unsatisfactory with a 5‐year survival rate of only 5‐10% [6]. Surgical resection offers no therapeutic benefit for patients diagnosed with advanced stages of ccRCC [7]. The mechanisms underlying the formation and progression of ccRCC should be elucidated, and novel therapeutic methods should be developed for the clinical management of patients with this malignancy

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