Huo Wei, Du Min, Pan Xinyan, Zhu Xiaomin, Gao Yu, Li Zhimin
Department of Medical Oncology Dalian Municipal Central Hospital China.
FEBS Open Bio. 2017 Jul 10;7(8):1085-1091. doi: 10.1002/2211-5463.12248. eCollection 2017 Aug.
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death. Cytokines, including interleukin 24 (IL-24), play an important role in HCC. IL-24 inhibits HCC metastasis but the molecular mechanism by which this occurs is still unknown. MicroRNAs (miRNAs) are regulators of cancers including hepatocellular carcinoma (HCC). However, the role that miRNAs play in the regulation of IL-24 in HCC is unclear. The aim of this study was to investigate the effects of regulation of IL-24 by miR-203a-3p.1 on liver cancer cell proliferation and metastasis. IL-24 mRNA and miR-203a-3p.1 were detected by real-time RT-PCR, and IL-24 protein in the cell growth medium was measured by ELISA. A luciferase assay was used to verify that the IL-24 gene was the target of miR-203a-3p.1. Cell survival ability was detected by the MTT assay and colony formation. Cell metastasis was assayed by the Transwell system. The results showed that IL-24 could be down-regulated by miR-203a-3p.1 in HCC cells and that miR-203a-3p.1 acted as an onco-miRNA by targeting IL-24. Inhibition of miR-203a-3p.1 in cells could lead to the reversal of HCC cell proliferation and metastasis. The study highlights a novel molecular interaction between miR-203a-3p.1 and IL-24, which indicates that IL-24 and miR-203a-3p.1 may constitute potential therapeutic targets for HCC.
肝细胞癌(HCC)是癌症相关死亡的最常见原因之一。细胞因子,包括白细胞介素24(IL-24),在HCC中发挥重要作用。IL-24抑制HCC转移,但其发生的分子机制仍不清楚。微小RNA(miRNA)是包括肝细胞癌(HCC)在内的癌症的调节因子。然而,miRNA在HCC中对IL-24的调节作用尚不清楚。本研究的目的是探讨miR-203a-3p.1对IL-24的调节作用对肝癌细胞增殖和转移的影响。通过实时RT-PCR检测IL-24 mRNA和miR-203a-3p.1,并通过ELISA检测细胞生长培养基中的IL-24蛋白。使用荧光素酶报告基因检测来验证IL-24基因是miR-203a-3p.1的靶标。通过MTT法和集落形成检测细胞存活能力。通过Transwell系统检测细胞转移。结果表明,miR-203a-3p.1可下调HCC细胞中的IL-24,且miR-203a-3p.1通过靶向IL-24发挥癌基因miRNA的作用。抑制细胞中的miR-203a-3p.1可导致HCC细胞增殖和转移的逆转。该研究突出了miR-203a-3p.1与IL-24之间的新型分子相互作用,这表明IL-24和miR-203a-3p.1可能构成HCC的潜在治疗靶点。