Yuan Chao, Su Zhenhong, Liao Shengjie, Li Duanzhuo, Zhou Zhiwen, Wang Yawen, Quan Mingchun, Zeng Lingling, Lv Cai, Shen Chenyi, Gong Weida, Wu Jianfeng, Chen Xiaogang, Hu Wenbing, Lv Xu, Si Wenxia, Yu Xin
Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University School of Medicine, Xialu District guilin north, road no. 16, Huangshi, 435003, Hubei, China.
Department of Urology, Haikou Municipal Hospital, Haikou, 570208, Hainan, China.
Cancer Cell Int. 2021 Jul 21;21(1):390. doi: 10.1186/s12935-021-02092-7.
miR-198 is involved in the formation, migration, invasion, and metastasis of various malignant cancers. However, the function and mechanism of action of miR-198 in the tumorigenesis of renal cell carcinoma (RCC) remain elusive. Here, we aimed to explore the role of miR198 in RCC.
Immunohistochemistry was performed to estimate the level of survivin in RCC sections. Quantitative real-time polymerase chain reaction was performed to determine the expression level of miR-198 in fresh RCC tissues. Furthermore, the target relationship between miR-198 and BIRC5 was predicted using the TargetScanHuman 7.2 database and verified via dual-luciferase reporter assay and western blotting. The effects of miR-198 on the viability, apoptosis, invasion, and migration of A498 and ACHN cells were studied using Cell Counting Kit-8, flow cytometry, transwell migration assay, and wound healing assay, respectively. Additionally, a xenograft nude mouse model was established to evaluate the effect of miR-198 on RCC tumorigenesis.
The expression levels of BIRC5 and miR-198 were respectively higher and lower in RCC tissues than those in normal adjacent tissues. Furthermore, miR-198 could inhibit luciferase activity and reduce the protein level of survivin without affecting the BIRC5 mRNA levels. miR-198 inhibited cell viability, migration, and invasion and promoted cell apoptosis; co-transfection with BIRC5 could rescue these effects. Moreover, miR-198 could repress tumor growth in the xenograft nude mouse model of RCC.
Our study demonstrates that miR-198 suppresses RCC progression by targeting BIRC5.
miR - 198参与多种恶性肿瘤的形成、迁移、侵袭和转移。然而，miR - 198在肾细胞癌（RCC）肿瘤发生中的功能和作用机制仍不清楚。在此，我们旨在探讨miR - 198在RCC中的作用。
采用免疫组织化学法评估RCC切片中生存素的水平。采用定量实时聚合酶链反应法测定新鲜RCC组织中miR - 198的表达水平。此外，使用TargetScanHuman 7.2数据库预测miR - 198与BIRC5之间的靶标关系，并通过双荧光素酶报告基因测定和蛋白质印迹法进行验证。分别使用细胞计数试剂盒 - 8、流式细胞术、Transwell迁移试验和伤口愈合试验研究miR - 198对A498和ACHN细胞活力、凋亡、侵袭和迁移的影响。此外，建立异种移植裸鼠模型以评估miR - 198对RCC肿瘤发生的影响。
RCC组织中BIRC5和miR - 198的表达水平分别高于和低于相邻正常组织。此外，miR - 198可抑制荧光素酶活性并降低生存素的蛋白质水平，而不影响BIRC5 mRNA水平。miR - 198抑制细胞活力、迁移和侵袭并促进细胞凋亡；与BIRC5共转染可挽救这些作用。此外，miR - 198可抑制RCC异种移植裸鼠模型中的肿瘤生长。
我们的研究表明，miR - 198通过靶向BIRC5抑制RCC进展。
