Department of Hepatobiliary-Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, China.
Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12131-12143. doi: 10.26355/eurrev_202012_24002.
Hepatocellular carcinoma (HCC) is an invasive malignant tumor with high mortality rate. Long non-coding RNA (lncRNA) MAFG-AS1 has been showed to play an oncogenic role in several malignant tumors. Nonetheless, the exact role of MAFG-AS1 in the progression of HCC has not been fully elucidated.
Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the mRNA and protein expression of MAFG-AS1 in HCC tissues and cells. Cell counting kit-8 (CCK-8), transwell and tubule formation assays were applied to uncover the proliferation, migration, invasion and tumor angiogenesis of HCC cells, respectively. RNA binding protein immunoprecipitation (RIP) assay and Luciferase reporter gene assay were employed to explore the molecular mechanism. In addition, Xenograft assay was used to investigate the effect of MAFG-AS1 in vivo.
MAFG-AS1 was highly expressed in HCC tissues and cells. Attenuation of MAFG-AS1 evidently suppressed the proliferation, migration, invasion and tumor angiogenesis of HCC cells, suggesting that MAFG-AS1 played an oncogenic role in HCC. MiR-3196 was sponged by MAFG-AS1, and OTX1 was a downstream target of miR-3196 in HCC. In addition, OTX1 expression was negatively associated with miR-3196 but positively associated with MAFG-AS1 in HCC tissues. Overexpression of OTX1 could abolish the repressive influence of MAFG-AS1 inhibition on the proliferation, migration, invasion and tumor angiogenesis of HCC cells.
MAFG-AS1 facilitated the progression of HCC via targeting miR-3196/OTX1 axis, which might be used as a new insight for HCC treatment.
肝细胞癌（HCC）是一种具有高死亡率的侵袭性恶性肿瘤。长链非编码 RNA（lncRNA）MAFG-AS1 在几种恶性肿瘤中发挥致癌作用。然而，MAFG-AS1 在 HCC 进展中的确切作用尚未完全阐明。
实时定量聚合酶链反应（RT-qPCR）和 Western blot 用于检测 HCC 组织和细胞中 MAFG-AS1 的 mRNA 和蛋白表达。细胞计数试剂盒-8（CCK-8）、Transwell 和管形成测定分别用于揭示 HCC 细胞的增殖、迁移、侵袭和肿瘤血管生成。RNA 结合蛋白免疫沉淀（RIP）测定和荧光素酶报告基因测定用于探索分子机制。此外，还使用异种移植实验来研究 MAFG-AS1 在体内的作用。
MAFG-AS1 在 HCC 组织和细胞中高表达。抑制 MAFG-AS1 显著抑制 HCC 细胞的增殖、迁移、侵袭和肿瘤血管生成，表明 MAFG-AS1 在 HCC 中发挥致癌作用。MAFG-AS1 可以吸附 miR-3196，而 OTX1 是 HCC 中 miR-3196 的下游靶点。此外，在 HCC 组织中，OTX1 的表达与 miR-3196 呈负相关，与 MAFG-AS1 呈正相关。过表达 OTX1 可以消除 MAFG-AS1 抑制对 HCC 细胞增殖、迁移、侵袭和肿瘤血管生成的抑制作用。
MAFG-AS1 通过靶向 miR-3196/OTX1 轴促进 HCC 的进展，这可能为 HCC 的治疗提供新的思路。
