Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Nanchang University, 1 Mindle Road, Nanchang, Jiangxi, 330006, People's Republic of China.
Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, 83 Xinqiao Main Street, Chongqing, 400000, People's Republic of China.
Mol Cancer. 2022 Mar 11;21(1):72. doi: 10.1186/s12943-022-01529-5.
Although the prognostic outcomes of liver cancer (LC) cases have improved with the advancement in diagnostic technology and treatment methods, the transferability and recurrence of HCC and the 5-year and 10-year survival rates of patients have remained unsatisfactory. As a result, there is a need for more accurate diagnostic indicators that can detect liver cancer early, effectively improving the prognosis of patients. Whole-genome sequencing (WGS) revealed that circ-ZEB1 and PIK3CA are highly expressed in HCC tissues, whereas miR-199a-3p is significantly downregulated in HCC. Multiple databases search and biological analysis revealed that elevated expression of circ-ZEB1 and PIK3CA was related to poor prognosis of HCC. In vitro and in vivo studies revealed that upregulated levels of PIK3CA and circ-ZEB1 were closely associated with HCC proliferation and apoptosis. Based on these results, we believe that circ-ZEB1 and PIK3CA could be used as biomarkers to diagnose and treat patients with HCC. More importantly, circ-ZEB1 can promotes the expression of PIK3CA by silencing miR-199a-3p and affecting the progression of HCC.
Postoperative specimens from 56 patients with HCC who had not undergone chemotherapy from 2015 to 2018 were collected from the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Nanchang University. WGS revealed differential expression of genes in HCC. Furthermore, RT-qPCR detected the expression of circ-ZEB1, miR-199a-3p, and PIK3CA in HCC tissues. MTT, EdU, and plate cloning experiments were conducted to detect cell proliferation, whereas flow cytometry analysis was used to detect apoptosis. FISH was used to co-localize circ-ZEB1 and miR-199a-3p, and biotin-coupled probe pull-down assay was used to detect the specific binding of circ-ZEB1 and miR-199a-3p. The dual-luciferase report assay detected the association of miR-199a-3p with PIK3CA. Western blotting was used to study the expression of PIK3CA protein. Circ-ZEB1 and PIK3CA were upregulated in HCC and predicted a poor prognosis. MiR-199a-3p showed low expression in HCC, whereas downregulation of circ-ZEB1 reduced HCC cell proliferation and promoted cell apoptosis. MiR-199a-3p blocked the effect of circ-ZEB1 on HCC. Circ-ZEB1 served as a biomarker of HCC. Circ-ZEB1 promoted the expression of PIK3CA by silencing miR-199a-3p to affect the progress of HCC.
Circ-ZEB1 promoted the expression of PIK3CA by depleting miR-199a-3p, thereby affecting HCC proliferation and apoptosis.
尽管随着诊断技术和治疗方法的进步，肝癌（LC）病例的预后有所改善，但 HCC 的转移和复发以及患者的 5 年和 10 年生存率仍不尽如人意。因此，需要更准确的诊断指标，以便早期发现肝癌，有效改善患者的预后。全基因组测序（WGS）显示，circ-ZEB1 和 PIK3CA 在 HCC 组织中高表达，而 miR-199a-3p 在 HCC 中显著下调。多个数据库搜索和生物分析表明，circ-ZEB1 和 PIK3CA 的高表达与 HCC 的不良预后有关。体外和体内研究表明，PIK3CA 和 circ-ZEB1 的上调水平与 HCC 的增殖和凋亡密切相关。基于这些结果，我们认为 circ-ZEB1 和 PIK3CA 可以作为诊断和治疗 HCC 患者的生物标志物。更重要的是，circ-ZEB1 通过沉默 miR-199a-3p 促进 PIK3CA 的表达，并影响 HCC 的进展。
2015 年至 2018 年间，南昌大学第二附属医院肝胆外科收集了 56 例未经化疗的 HCC 患者的术后标本。WGS 显示 HCC 中基因的差异表达。此外，RT-qPCR 检测 HCC 组织中 circ-ZEB1、miR-199a-3p 和 PIK3CA 的表达。MTT、EdU 和平板克隆实验用于检测细胞增殖，而流式细胞术分析用于检测细胞凋亡。FISH 用于共定位 circ-ZEB1 和 miR-199a-3p，生物素偶联探针下拉实验用于检测 circ-ZEB1 和 miR-199a-3p 的特异性结合。双荧光素酶报告实验检测 miR-199a-3p 与 PIK3CA 的关联。Western blot 用于研究 PIK3CA 蛋白的表达。Circ-ZEB1 和 PIK3CA 在 HCC 中上调，并预测预后不良。miR-199a-3p 在 HCC 中低表达，而 circ-ZEB1 下调可降低 HCC 细胞增殖并促进细胞凋亡。miR-199a-3p 阻断了 circ-ZEB1 对 HCC 的作用。Circ-ZEB1 是 HCC 的生物标志物。Circ-ZEB1 通过沉默 miR-199a-3p 促进 PIK3CA 的表达，从而影响 HCC 的增殖和凋亡。
Circ-ZEB1 通过耗尽 miR-199a-3p 促进 PIK3CA 的表达，从而影响 HCC 的增殖和凋亡。
