Department of Liver Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
J Cell Biochem. 2020 Nov;121(11):4419-4430. doi: 10.1002/jcb.29665. Epub 2020 Feb 14.
Kinesin family member 2C (KIF2C), a substantial mitotic regulator, has been verified to exert a malignant function in several cancers. However, its function in hepatocellular carcinoma (HCC) remains unclear. In this study, the expression profile of KIF2C in HCC was characterized through the dataset from the TCGA and clinical tissue microarrays containing 220 pairs of resected HCC tissues and adjacent nontumor tissues in our hospital. The results indicated that KIF2C was substantially higher expression in tumor tissues than adjacent nontumor tissues. High expression of KIF2C significantly correlated with large tumor (>5.0 cm) (P = .001) and implied a dismal postoperative overall survival (OS) (hazard ratio [HR] = 1.729; P = .002) in our cohort of patients. Gain and loss of function assays displayed that KIF2C promoted HCC cell proliferation, accelerated cell cycle progression, and impeded apoptosis. By bioinformatic tools and mechanistic investigation, we found that KIF2C interacted with various cell-cycle-related proteins and was significantly involved in growth-promoting pathways. KIF2C upregulated PCNA and CDC20 expression. Subsequently, we investigated the regulation of KIF2C by competing endogenous RNA and elucidated that has-miR-6715a-3p was directly bond to the 3'-untranslated region of KIF2C through dual luciferase assays, thereby inhibiting KIF2C expression. Furthermore, the long noncoding RNA GS1-358P8.4 was found to be a candidate of KIF2C for has-miR-6715a-3p binding. HCC patients with high lncRNA-GS1-358P8.4 expression had shorter OS and relapse-free survival compared to those with low expression, which was accordance with the KIF2C. Taken together, KIC2C aggravated HCC progression, it could serve as a prognostic indicator and confer a novel target for clinical treatment.
驱动蛋白家族成员 2C（KIF2C）是一种重要的有丝分裂调节剂，已被证实其在几种癌症中发挥恶性作用。然而，其在肝细胞癌（HCC）中的功能尚不清楚。在这项研究中，通过 TCGA 数据集和包含我院 220 对切除 HCC 组织和相邻非肿瘤组织的临床组织微阵列，对 HCC 中 KIF2C 的表达谱进行了描述。结果表明，KIF2C 在肿瘤组织中的表达明显高于相邻非肿瘤组织。KIF2C 的高表达与大肿瘤（>5.0cm）显著相关（P=0.001），并且在我们的患者队列中提示术后总体生存（OS）不良（危险比[HR]＝1.729；P=0.002）。获得和丧失功能试验显示，KIF2C 促进 HCC 细胞增殖，加速细胞周期进程，并抑制细胞凋亡。通过生物信息学工具和机制研究，我们发现 KIF2C 与多种细胞周期相关蛋白相互作用，并显著参与促进生长的途径。KIF2C 上调 PCNA 和 CDC20 的表达。随后，我们研究了 KIF2C 被竞争性内源 RNA 调控的情况，并通过双荧光素酶报告基因实验发现，has-miR-6715a-3p 直接与 KIF2C 的 3'-非翻译区结合，从而抑制 KIF2C 的表达。此外，还发现长链非编码 RNA GS1-358P8.4 是 KIF2C 与 has-miR-6715a-3p 结合的候选物。与低表达的 HCC 患者相比，高表达 lncRNA-GS1-358P8.4 的 HCC 患者的总生存（OS）和无复发生存（RFS）更短，这与 KIF2C 的情况一致。总之，KIF2C 加重了 HCC 的进展，它可以作为一个预后指标，并为临床治疗提供一个新的靶点。
