MicroRNA-505 negatively regulates HMGB1 to suppress cell proliferation in renal cell carcinoma.

Abstract

microRNAs have been recognized to regulate a wide range of biology of renal cell carcinoma (RCC). Although miR‐505 has been reported to play as a suppressor in several human tumors, the physiological function of miR‐505 in RCC still remain unknown. Therefore, the role of miR‐505 and relevant regulatory mechanisms were investigated in RCC in this study. Quantitative real‐time polymerase chain reaction was conducted to detect the expression of miR‐505 and high mobility group box 1 (HMGB1) in both RCC tissues and cell lines. Immunohistochemical staining was used to assess the correlation between HMGB1 expression and PCNA expression in RCC tissues. Subsequently, the effects of miR‐505 on proliferation were determined in vitro using cell counting kit‐8 proliferation assays and 5‐ethynyl‐2′‐deoxyuridine incorporation. The molecular mechanism underlying the relevance between miR‐505 and HMGB1 was confirmed by luciferase assay. Xenograft tumor formation was used to reflect the proliferative capacity of miR‐505 in vivo experiments. Overall, a relatively lower miR‐505 and higher HMGB1 expression in RCC specimens and cell lines were found. HMGB1 was verified as a direct target of miR‐505 by luciferase assay. In vitro, overexpression of miR‐505 negatively regulates HMGB1 to suppress the proliferation in Caki‐1; meanwhile, knock‐down of miR‐505 negatively regulates HMGB1 to promote the proliferation in 769P. In addition, in vivo overexpression of miR‐505 could inhibit tumor cell proliferation in RCC by xenograft tumor formation. Therefore, miR‐505, as a tumor suppressor, negatively regulated HMGB1 to suppress the proliferation in RCC, and might serve as a novel therapeutic target for RCC clinical treatment.