Department of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
J Gene Med. 2023 Dec;25(12):e3562. doi: 10.1002/jgm.3562. Epub 2023 Jun 30.
Accumulating research findings have shown that circular RNAs (circRNAs) play an indispensable role in tumorigenesis and tumor progression. The current study aimed to explore the role and modulatory mechanism of hsa_circ_0003596 in clear cell renal cell carcinoma (ccRCC). Quantitative real-time polymerase chain reaction was adopted to detect the expression of hsa_circ_0003596 in ccRCC tissue and cell lines. 5-Ethynyl-2'-deoxyuridine, cell counting kit 8 and the colony formation assay were utilized to assess the proliferation potential of the ccRCC cells. Transwell along with wound healing assays were adopted to quantify infiltration coupled with the migration potential of the cells. The current research study found that the circRNA hsa_circ_0003596 was overexpressed in ccRCC tissue and cell lines. Further, result showed that hsa_circ_0003596 was associated with distant metastasis of renal cancer. Notably, the knockdown of hsa_circ_0003596 can lower the proliferation, infiltration and migration potential of ccRCC cells. The results of in vivo experiments found that the reduction of hsa_circ_0003596 significantly hampered the growth of tumors in mice. In addition, it was evident that hsa_circ_0003596 acts as a "molecular sponge" for miR-502-5p to upregulate the expression of the microRNA-502-5p (miR-502-5p) target insulin-like growth factor 1 (IGF1R). Furthermore, it was found that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling was the downstream cascade of hsa_circ_0003596/miR-502-5p/IGF1R cascade, which is partly responsible for the cancer-promoting effect. Overall, the results of the present study showed that hsa_circ_0003596 facilitated the proliferation, infiltration and migration of ccRCC through the miR-502-5p/IGF1R/PI3K/AKT axis. Therefore, it was evident that hsa_circ_0003596 can serve as a possible biomarker and therapeutic target against ccRCC.
越来越多的研究结果表明,环状 RNA(circRNA)在肿瘤发生和肿瘤进展中起着不可或缺的作用。本研究旨在探讨 hsa_circ_0003596 在透明细胞肾细胞癌(ccRCC)中的作用及其调节机制。采用实时定量聚合酶链反应检测 hsa_circ_0003596 在 ccRCC 组织和细胞系中的表达。采用 5-乙炔基-2'-脱氧尿苷、细胞计数试剂盒 8 和集落形成实验评估 ccRCC 细胞的增殖潜力。采用 Transwell 及划痕愈合实验来量化细胞的浸润和迁移潜力。本研究发现环状 RNA hsa_circ_0003596 在 ccRCC 组织和细胞系中表达上调。此外,研究结果表明 hsa_circ_0003596 与肾癌的远处转移有关。值得注意的是,hsa_circ_0003596 的敲低可以降低 ccRCC 细胞的增殖、浸润和迁移能力。体内实验结果发现,hsa_circ_0003596 的减少显著抑制了小鼠肿瘤的生长。此外,hsa_circ_0003596 作为 miR-502-5p 的“分子海绵”,上调了 miR-502-5p 靶基因胰岛素样生长因子 1(IGF1R)的表达。此外,研究发现磷脂酰肌醇 3-激酶(PI3K)/AKT 信号通路是 hsa_circ_0003596/miR-502-5p/IGF1R 级联的下游级联,部分负责促进癌症的发生。综上所述,本研究结果表明,hsa_circ_0003596 通过 miR-502-5p/IGF1R/PI3K/AKT 轴促进 ccRCC 的增殖、浸润和迁移。因此,hsa_circ_0003596 可能成为 ccRCC 潜在的生物标志物和治疗靶点。
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