Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China.
Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China.
Microvasc Res. 2021 Mar;134:104120. doi: 10.1016/j.mvr.2020.104120. Epub 2020 Dec 11.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death around the world. Despite improvement in the prevention and treatment of HCC, the clinical prognosis is still poor with increasing mortality. Non-coding RNAs play pivotal roles in HCC oncogenesis, but the detailed mechanism is poorly known. Therefore, the functions and interaction of lncRNA NORAD and miR-211-5p in HCC was investigated in this study.
Quantitative real-time PCR method was used to analyze the expression of NORAD and miR-211-5p in clinical HCC tissues and cultured cell lines. Knockdown of NORAD and overexpression of miR-211-5p were then carried in HCC cells. Moreover, bioinformatics analysis and luciferase report assays were further employed to analyze the interaction between miR-211-5p and NORAD or FOXD1.
Increased lncRNA NORAD and decreased miR-211-5p expression were first detected in HCC compared with the peritumorial area. Further studies showed that knockdown of NORAD or overexpression of miR-211-5p impaired the proliferation, migration and angiogenesis of HCC cells. Mechanistically, we found that NORAD functions as a sponge for miR-211-5p. Moreover, it was revealed that decreased miR-211-5p induced the expression of FOXD1 as well as its downstream target VEGF-A, thereby contributes to enhanced angiogenesis of HCC.
Elevated NORAD works as a sponge for miR-211-5p in HCC, thus release the inhibition effect of the latter on its downstream target FOXD1 and VEGF-A, which finally promotes angiogenesis. These results provide new insights into the interaction between NORAD and miR-211-5p in HCC and their potential usage as targets for the development of novel therapeutics against HCC.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。尽管在 HCC 的预防和治疗方面取得了进展，但临床预后仍然较差，死亡率不断上升。非编码 RNA 在 HCC 发生中发挥着关键作用，但详细机制尚不清楚。因此，本研究探讨了 lncRNA NORAD 和 miR-211-5p 在 HCC 中的功能和相互作用。
采用实时定量 PCR 方法分析临床 HCC 组织和培养细胞系中 NORAD 和 miR-211-5p 的表达。然后在 HCC 细胞中敲低 NORAD 并过表达 miR-211-5p。此外，还进一步采用生物信息学分析和荧光素酶报告试验分析 miR-211-5p 与 NORAD 或 FOXD1 的相互作用。
首先在 HCC 中检测到 lncRNA NORAD 表达增加，miR-211-5p 表达降低，与肿瘤周围区域相比。进一步的研究表明，敲低 NORAD 或过表达 miR-211-5p 可抑制 HCC 细胞的增殖、迁移和血管生成。从机制上讲，我们发现 NORAD 作为 miR-211-5p 的海绵发挥作用。此外，研究表明，miR-211-5p 表达下调可诱导 FOXD1 及其下游靶基因 VEGF-A 的表达，从而促进 HCC 的血管生成。
升高的 NORAD 在 HCC 中作为 miR-211-5p 的海绵发挥作用，从而释放后者对其下游靶基因 FOXD1 和 VEGF-A 的抑制作用，最终促进血管生成。这些结果为 NORAD 和 miR-211-5p 在 HCC 中的相互作用及其作为开发新型 HCC 治疗方法的靶点提供了新的见解。
