Let-7g 靶向胶原类型 I 阿尔法 2 并抑制肝癌细胞迁移。
Let-7g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma.
机构信息
Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Centre for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
出版信息
J Hepatol. 2010 May;52(5):690-7. doi: 10.1016/j.jhep.2009.12.025. Epub 2010 Mar 1.
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis mainly due to metastasis. MicroRNAs are endogenous small noncoding RNAs that regulate cellular gene expression and are functionally linked to tumourigenesis. Using microarray analysis, we recently identified 20 miRNAs associated with HCC metastasis. Here, we carried out further analyses on one of these microRNAs, let-7g, to determine whether it is functionally linked to HCC metastasis.
METHODS
Quantitative real-time polymerase chain reaction was used to determine the level of mature let-7g transcript in HCC clinical specimens and its correlation with patient survival. Ectopic expression of let-7g was carried out in HCC cell lines to assess its influence on cell growth, migration, and invasion.
RESULTS
We confirmed that the level of let-7g was significantly lower in metastatic HCCs compared to metastasis-free HCCs. Moreover, low let-7g expression in a tumour was predictive of poor survival in HCC patients. Functional studies indicated that ectopic expression of let-7g significantly inhibits HCC cell migration and cell growth. In-silico analysis revealed members of soluble collagens as potential targets of let-7g. Consistently, the levels of type I collagen alpha2 (COL1A2) and let-7g were inversely correlated in HCC clinical specimens. COL1A2 was experimentally validated as a direct target of let-7g. Moreover, addition of COL1A2 counteracted the inhibitory effect of let-7g on cell migration.
CONCLUSIONS
These results suggest that let-7g may suppress HCC metastasis partially through targeting COL1A2.
背景与目的
肝细胞癌（HCC）是一种侵袭性癌症，预后较差，主要是由于转移。miRNAs 是内源性的小非编码 RNA，调节细胞基因表达，与肿瘤发生功能相关。我们最近使用微阵列分析发现了 20 个与 HCC 转移相关的 miRNAs，在此，我们对其中一个 miRNA（let-7g）进行了进一步分析，以确定其是否与 HCC 转移功能相关。
方法
使用定量实时聚合酶链反应（PCR）确定 HCC 临床标本中成熟 let-7g 转录本的水平及其与患者生存的相关性。在 HCC 细胞系中外源性表达 let-7g，以评估其对细胞生长、迁移和侵袭的影响。
结果
我们证实转移性 HCC 中 let-7g 的水平明显低于无转移 HCC。此外，肿瘤中 let-7g 表达水平低预示 HCC 患者生存不良。功能研究表明，let-7g 的异位表达可显著抑制 HCC 细胞的迁移和生长。计算机分析显示可溶性胶原蛋白成员可能是 let-7g 的潜在靶标。一致地，HCC 临床标本中 COL1A2 与 let-7g 的水平呈负相关。COL1A2 被实验验证为 let-7g 的直接靶标。此外，添加 COL1A2 可抵消 let-7g 对细胞迁移的抑制作用。
结论
这些结果表明，let-7g 可能通过靶向 COL1A2 抑制 HCC 转移。
Zotero 插件