环状 WHSC1 作为癌基因促进肝细胞癌进展。
CircWHSC1 serves as an oncogene to promote hepatocellular carcinoma progression.
机构信息
Department of General Surgery, Shanxi Provincial Cancer Hospital, Taiyuan City, Shanxi Province, China.
Department of hepatobiliary surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan City, Shanxi Province, China.
出版信息
Eur J Clin Invest. 2021 Jun;51(6):e13487. doi: 10.1111/eci.13487. Epub 2021 Apr 27.
BACKGROUND
Circular RNAs (circRNAs) function as vital regulators in multifarious cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNA Wolf-Hirschhorn syndrome candidate gene-1 (circWHSC1) in HCC are barely known.
METHODS
Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted for the levels of circWHSC1, miR-142-3p, miR-421, miR-665 and homeobox A1 (HOXA1) mRNA. Cell Counting Kit-8 (CCK-8) assay, colony formation assay and 5'-ethynyl-2'-deoxyuridine (EdU) assay were used to evaluate cell proliferation ability. Transwell assay was adopted for cell migration and invasion. Western blot assay was employed for protein levels. RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were executed to verify the interaction between miR-142-3p and circWHSC1 or HOXA1. Murine xenograft model assay was conducted for the role of circWHSC1 in vivo. The morphology of exosomes was observed by transmission electron microscopy (TEM).
RESULTS
CircWHSC1 was elevated in HCC tissues and cells, and high level of circWHSC1 was associated with worse overall survival of HCC patients. Knockdown of circWHSC1 suppressed HCC cell proliferation and metastasis in vitro and restrained tumorigenesis in vivo. CircWHSC1 functioned as the sponge for miR-142-3p, which directly targeted HOXA1. Inhibition of miR-142-3p ameliorated the effects of circWHSC1 knockdown on HCC cell proliferation and metastasis. Moreover, miR-142-3p overexpression restrained the growth and motility of HCC cells, with HOXA1 elevation reversing the impacts. Additionally, circWHSC1 was increased in HCC patients' serum and might be a diagnostic indicator for HCC.
CONCLUSION
CircWHSC1 played a tumour-promoting role in HCC by elevating HOXA1 through sponging miR-142-3p.
背景
环状 RNA（circRNA）在多种癌症中作为重要的调节因子发挥作用，包括肝细胞癌（HCC）。然而，Wolf-Hirschhorn 综合征候选基因 1（circWHSC1）环状 RNA 在 HCC 中的作用知之甚少。
方法
采用实时定量聚合酶链反应（qRT-PCR）检测 circWHSC1、miR-142-3p、miR-421、miR-665 和同源盒 A1（HOXA1）mRNA 的水平。使用细胞计数试剂盒-8（CCK-8）检测、集落形成检测和 5'-乙炔基-2'-脱氧尿苷（EdU）检测评估细胞增殖能力。采用 Transwell 检测细胞迁移和侵袭。采用 Western blot 检测蛋白水平。采用 RNA 下拉实验、双荧光素酶报告实验和 RNA 免疫沉淀（RIP）实验验证 miR-142-3p 与 circWHSC1 或 HOXA1 的相互作用。进行小鼠异种移植模型实验以研究 circWHSC1 在体内的作用。采用透射电子显微镜（TEM）观察外泌体的形态。
结果
circWHSC1 在 HCC 组织和细胞中上调，高水平的 circWHSC1与 HCC 患者总体生存率较差相关。circWHSC1 敲低抑制 HCC 细胞在体外的增殖和转移，并抑制体内肿瘤发生。circWHSC1 作为 miR-142-3p 的海绵，直接靶向 HOXA1。抑制 miR-142-3p 可改善 circWHSC1 敲低对 HCC 细胞增殖和转移的影响。此外，miR-142-3p 过表达抑制 HCC 细胞的生长和运动，HOXA1 升高可逆转这些影响。此外，circWHSC1 在 HCC 患者的血清中增加，可能是 HCC 的诊断指标。
结论
circWHSC1 通过海绵吸附 miR-142-3p 升高 HOXA1 在 HCC 中发挥促瘤作用。
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