Department of Interventional, Harbin Medical University Cancer Hospital, Harbin 150040, China.
Department of Gerontology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Acta Biochim Biophys Sin (Shanghai). 2020 Mar 18;52(3):302-309. doi: 10.1093/abbs/gmz167.
Hepatocellular carcinoma (HCC) is the most prominent form of presentation in liver cancer. It is also the fourth most common cause of cancer-associated deaths globally. The role of nucleus accumbens associated protein-1 (NACC-1) has been evaluated in several cancers. This protein is a transcriptional regulator that regulates a number of significant cellular processes. In the current study, we aimed to understand the role of NACC-1 in HCC. Primarily, we measured the expression of NACC-1 using quantitative real time polymerase chain reaction and western blot analysis. We knocked down the expression of NACC-1 in HCC cell lines Huh7 and HepG2 by transferring a commercially synthesized small interfering RNA and explored the impact of NACC-1 knockdown on cellular growth, migration, invasion, and chemoresistance to doxorubicin. Through bioinformatic analysis, we identified NACC-1 as a potential target of miR-760. Using a dual reporter luciferase assay, we confirmed the predicted target and assessed miR-760-mediated regulation of NACC-1 and rescue of tumorigenic phenotypes. We observed increased expression of NACC-1 in HCC. Furthermore, knockdown of NACC-1 resulted in reduced cell proliferation and invasion and increased susceptibility to doxorubicin-mediated chemosensitivity. Overexpression of miR-760 in HCC cell lines rescued NACC-1-mediated migration and invasion. We revealed that miR-760 regulated NACC-1 expression in HCC. Our data indicated that both miR-760 and NACC-1 could be used as prognostic markers, and miR-760 may have therapeutic benefits for HCC and other cancers.
肝细胞癌（HCC）是肝癌最常见的表现形式。它也是全球癌症相关死亡的第四大主要原因。伏隔核相关蛋白-1（NACC-1）在几种癌症中的作用已经得到了评估。这种蛋白质是一种转录调节剂，可调节许多重要的细胞过程。在本研究中，我们旨在了解 NACC-1 在 HCC 中的作用。首先，我们使用定量实时聚合酶链反应和 Western blot 分析来测量 NACC-1 的表达。我们通过转染商业合成的小干扰 RNA 来敲低 HCC 细胞系 Huh7 和 HepG2 中的 NACC-1 表达，并探讨 NACC-1 敲低对细胞生长、迁移、侵袭和对多柔比星的化学耐药性的影响。通过生物信息学分析，我们将 NACC-1 鉴定为 miR-760 的潜在靶标。通过双报告荧光素酶测定，我们验证了预测的靶标，并评估了 miR-760 对 NACC-1 的调节作用和对肿瘤发生表型的挽救作用。我们观察到 HCC 中 NACC-1 的表达增加。此外，NACC-1 的敲低导致细胞增殖和侵袭减少，并且对多柔比星介导的化学敏感性增加。在 HCC 细胞系中过表达 miR-760 挽救了 NACC-1 介导的迁移和侵袭。我们揭示了 miR-760 调节 HCC 中的 NACC-1 表达。我们的数据表明，miR-760 和 NACC-1 均可作为预后标志物，并且 miR-760 可能对 HCC 和其他癌症具有治疗益处。
