Hsa_circ_0001756 通过调节 IGF2BP2 介导的 RAB5A 表达和 EGFR/MAPK 信号通路促进卵巢癌细胞进展。
Hsa_circ_0001756 promotes ovarian cancer progression through regulating IGF2BP2-mediated RAB5A expression and the EGFR/MAPK signaling pathway.
机构信息
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Gynecology, The Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China.
出版信息
Cell Cycle. 2022 Apr;21(7):685-696. doi: 10.1080/15384101.2021.2010166. Epub 2022 Feb 3.
Hsa_circ_0001756 was reported to be upregulated in serum samples of ovarian cancer (OC) patients and may serve as a potential OC biomarker. This study aimed to investigate the role and molecular mechanisms of hsa_circ_0001756 in OC procession. Herein, we detected the expression of hsa_circ_0001756 in OC tissues and cell lines with RT-qPCR assay, which showed that hsa_circ_0001756 was upregulated in OC tissues and cell lines. Then small interfering RNA targeting hsa_circ_0001756 (si-hsa_circ_0001756) was transfected into SKOV3 and A2780 cells, and the proliferation, invasion, and expression of epithelial-mesenchymal transition (EMT) marker proteins were determined with CCK-8, Transwell and Western blotting assays, respectively. We found that hsa_circ_0001756 knockdown inhibited OC cell proliferation, invasion and EMT. Moreover, RNA pull-down assay verified the binding between hsa_circ_0001756 and IGF2 mRNA binding protein 2 (IGF2BP2), and rescue experiments indicated that IGF2BP2 overexpression reversed the effects of has_circ_0001756 knockdown on OC cell functions. Co-IP assay verified IGF2BP2 could interact with RAB GTPase 5A (RAB5A) protein. Then SKOV3 cells were transfected with si-IGF2BP2 alone or together with pcDNA-RAB5A, followed by the detection of SKOV3 cell functions. We found that IGF2BP2 knockdown inhibited OC cell proliferation, invasion, and EMT, while RAB5A overexpression reversed these effects. Finally, SKOV3 cells transfected with si-hsa_circ_0001756 were injected into nude mice through tail vein. Hsa_circ_0001756 knockdown significantly inhibited the xenograft tumor growth of OC . In conclusion, hsa_circ_0001756 knockdown inhibits OC cell proliferation, invasion, and EMT, and reduces xenograft tumor growth by suppressing IGF2BP2-mediated RAB5A expression and blocking the EGFR/MAPK signaling pathway.
Hsa_circ_0001756 在卵巢癌 (OC) 患者的血清样本中被报道上调,可能作为潜在的 OC 生物标志物。本研究旨在探讨 hsa_circ_0001756 在 OC 进程中的作用和分子机制。在此,我们通过 RT-qPCR 检测 OC 组织和细胞系中 hsa_circ_0001756 的表达,结果表明 hsa_circ_0001756 在 OC 组织和细胞系中上调。然后,用靶向 hsa_circ_0001756 的小干扰 RNA (si-hsa_circ_0001756) 转染 SKOV3 和 A2780 细胞,分别用 CCK-8、Transwell 和 Western blot 检测细胞增殖、侵袭和上皮间质转化 (EMT) 标志物蛋白的表达。结果发现,hsa_circ_0001756 敲低抑制 OC 细胞增殖、侵袭和 EMT。此外,RNA 下拉实验验证了 hsa_circ_0001756 与胰岛素样生长因子 2 mRNA 结合蛋白 2 (IGF2BP2) 的结合,挽救实验表明 IGF2BP2 过表达逆转了 hsa_circ_0001756 敲低对 OC 细胞功能的影响。Co-IP 实验验证了 IGF2BP2 可以与 RAB GTPase 5A (RAB5A) 蛋白相互作用。然后,单独转染 SKOV3 细胞 si-IGF2BP2 或与 pcDNA-RAB5A 共转染,然后检测 SKOV3 细胞功能。结果发现,IGF2BP2 敲低抑制 OC 细胞增殖、侵袭和 EMT,而过表达 RAB5A 逆转了这些作用。最后,通过尾静脉向转染了 si-hsa_circ_0001756 的 SKOV3 细胞注射裸鼠。hsa_circ_0001756 敲低显著抑制 OC 的异种移植肿瘤生长。总之,hsa_circ_0001756 敲低通过抑制 IGF2BP2 介导的 RAB5A 表达和阻断 EGFR/MAPK 信号通路抑制 OC 细胞增殖、侵袭和 EMT,减少异种移植肿瘤生长。