LncRNA ITGB2-AS1 promotes the progression of clear cell renal cell carcinoma by modulating miR-328-5p/HMGA1 axis.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common histologic subtype of renal cell carcinoma and long non-coding RNAs (lncRNAs) play important roles in the progression of ccRCC. In this study, we aim to explore the potential function of ITGB2-AS1 in ccRCC progression and its underlying molecular mechanism. We first explored the association between ITGB2-AS1 expression level and ccRCC prognosis. We found that the expression level of ITGB2-AS1 was significantly higher in ccRCC tumor and cell lines, and highly expressed ITGB2-AS1 was also associated with a poorer prognosis. Consistently, silencing ITGB2-AS1 inhibited proliferation, promoted apoptosis in ccRCC cell lines, and curbed the tumorigenesis in the Xenograft model, reduced tumorigenesis in a xenograft tumor growth model. We further identified and confirmed the miRNA miR-328-5p as a target of ITGB2-AS1, and miR-328-5p negatively regulated the expression of HMGA1 protein. The anti-tumor effect of silencing ITGB2-AS1 could be partially rescued by inhibiting miR-328-5p activity or overexpressing HMGA1, indicating that ITGB2-AS1 promotes the survival and progression of ccRCC by modulating miR-328-5p/HMGA1 axis. Collectively, our data demonstrated that ITGB2-AS1 expression level is positively correlated with the survival and tumorigenesis of ccRCC. As a target of ITGB2-AS1, miR-328-5p seems to function as a tumor-suppressor, and the oncogenic effect of ITGB2-AS1 is partially mediated via the miR-328-5p/HMGA1 axis.