Department of Thoracic Surgery, The Second Affiliated Hospital of Wannan Medical College, No. 10 Kangfu Road, Jinghu District, Wuhu City, 241000, Anhui Province, China.
Dig Dis Sci. 2021 Dec;66(12):4374-4383. doi: 10.1007/s10620-020-06789-z. Epub 2021 Jan 13.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. CircZKSCAN1 (hsa_circ_0001727) was reported to be related to HCC development. The present study aims to elucidate the potential role and molecular mechanism of circZKSCAN1 in the regulation of HCC progression.
CircZKSCAN1, miR-873-5p, and downregulation of deleted in liver cancer 1 (DLC1) in HCC tissues and cells were detected by RT-qPCR. Correlation between circZKSCAN1 expression and overall survival rate was measured by Kaplan-Meier survival analysis. The effects of circZKSCAN1, miR-873-5p, and DLC1 on proliferation, migration, and invasion were analyzed by CCK-8 and transwell assays, respectively. CyclinD1, Matrix metalloproteinase (MMP)-9, MMP-2, and DLC1 in HCC cells were detected by Western blot assay. The binding relationship between miR-873-5p and circZKSCAN1 or DLC1 was predicted by the Circinteractome or Starbase, and then confirmed by dual-luciferase reporter assays, respectively. Tumor volume and tumor weight were measured in vivo.
CircZKSCAN1 was downregulated in HCC tissues and cells. Kaplan-Meier survival analysis suggested that there was a positive correlation between circZKSCAN1 expression and overall survival rate. Functionally, circZKSCAN1 blocked proliferation, migration, and invasion of HCC cells. MiR-873-5p was a target miRNA of circZKSCAN1, and miR-873-5p directly bound with DLC1. Rescue experiments confirmed that miR-873-5p overexpression or DLC1 knockdown attenuated the suppressive effects of circZKSCAN1 on HCC tumor growth in vitro. Besides, circZKSCAN1 inhibited HCC cell growth in vivo.
This study firstly revealed that circZKSCAN1 curbed HCC progression via modulating miR-873-5p/DLC1 axis, providing a potential therapeutic target for HCC treatment.
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。CircZKSCAN1（hsa_circ_0001727）已被报道与 HCC 的发展有关。本研究旨在阐明 circZKSCAN1 在调控 HCC 进展中的潜在作用和分子机制。
通过 RT-qPCR 检测 HCC 组织和细胞中的 circZKSCAN1、miR-873-5p 和下调的肝癌缺失基因 1（DLC1）。通过 Kaplan-Meier 生存分析测量 circZKSCAN1 表达与总生存率之间的相关性。通过 CCK-8 和 Transwell 测定分别分析 circZKSCAN1、miR-873-5p 和 DLC1 对增殖、迁移和侵袭的影响。Western blot 检测 HCC 细胞中的细胞周期蛋白 D1（CyclinD1）、基质金属蛋白酶（MMP）-9、MMP-2 和 DLC1。通过 Circinteractome 或 Starbase 预测 miR-873-5p 与 circZKSCAN1 或 DLC1 的结合关系，然后分别通过双荧光素酶报告基因测定进行验证。体内测量肿瘤体积和肿瘤重量。
CircZKSCAN1 在 HCC 组织和细胞中下调。Kaplan-Meier 生存分析表明，circZKSCAN1 表达与总生存率呈正相关。功能上，circZKSCAN1 抑制 HCC 细胞的增殖、迁移和侵袭。miR-873-5p 是 circZKSCAN1 的靶 miRNA，并且 miR-873-5p 直接与 DLC1 结合。挽救实验证实，miR-873-5p 过表达或 DLC1 敲低可减弱 circZKSCAN1 对 HCC 肿瘤体外生长的抑制作用。此外，circZKSCAN1 抑制 HCC 细胞在体内的生长。
本研究首次揭示 circZKSCAN1 通过调节 miR-873-5p/DLC1 轴抑制 HCC 进展，为 HCC 的治疗提供了一个潜在的治疗靶点。
