Zhang Wensheng, Lu Yigang, Shi Huibo, Li Xungang, Zhang Zhuo, Deng Xinxi, Yang Yang, Wan Bin
Department of Urology, The First People's Hospital of Jiujiang in Jiangxi Province, Affiliated Medical College of Jiujiang Hospital, Nanchang University, No. 48, Taling South Road, Xunyang District, Jiujiang City, 332000, Jiangxi Province, China.
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Hum Cell. 2021 Sep;34(5):1545-1557. doi: 10.1007/s13577-021-00563-7. Epub 2021 Jun 25.
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.
透明细胞肾细胞癌（ccRCC）是肾细胞癌最常见的组织学亚型，长链非编码RNA（lncRNAs）在ccRCC进展中发挥重要作用。在本研究中，我们旨在探讨ITGB2-AS1在ccRCC进展中的潜在功能及其潜在分子机制。我们首先探讨了ITGB2-AS1表达水平与ccRCC预后之间的关联。我们发现，ITGB2-AS1在ccRCC肿瘤组织和细胞系中的表达水平显著更高，且ITGB2-AS1高表达也与较差的预后相关。同样，沉默ITGB2-AS1可抑制ccRCC细胞系的增殖、促进其凋亡，并抑制异种移植模型中的肿瘤发生，减少异种移植肿瘤生长模型中的肿瘤发生。我们进一步鉴定并确认miRNA miR-328-5p是ITGB2-AS1的靶标，且miR-328-5p负向调节HMGA1蛋白的表达。抑制miR-328-5p活性或过表达HMGA1可部分挽救沉默ITGB2-AS1的抗肿瘤作用，这表明ITGB2-AS1通过调节miR-328-5p/HMGA1轴促进ccRCC的存活和进展。总体而言，我们的数据表明ITGB2-AS1表达水平与ccRCC的存活和肿瘤发生呈正相关。作为ITGB2-AS1的靶标，miR-328-5p似乎发挥肿瘤抑制作用，且ITGB2-AS1的致癌作用部分通过miR-328-5p/HMGA1轴介导。
