外泌体介导长链非编码RNA H19促进肝癌细胞增殖与转移

外泌体是由细胞分泌的直径为30～150 nm的小囊泡，含有丰富的mRNA、microRNA和长链非编码RNA(lncRNA)。目前，大多数外泌体研究都集中在mRNA和microRNA，而对lncRNA的生物学功能并不十分清楚。研究表明，肿瘤细胞外泌体 lncRNA H19在肿瘤细胞的增殖、迁移和侵袭中发挥了重要作用。本研究将筛选到的lncRNA H19高表达的肝癌细胞HCCLM3，分别收集其高表达lncRNA H19的外泌体和其下调lncRNA H19表达后的外泌体。然后，将收集到的外泌体分别添加到lncRNA H19低表达的肝癌细胞Hep3B和HepG2孵育液中。孵育24 h后，检测其对肿瘤细胞的增殖、迁移和侵袭能力的影响。结果显示，肝癌细胞HCCLM3可分泌大量的外泌体，且能被其他肿瘤细胞大量摄取；与下调lncRNA H19表达的外泌体相比，lncRNA H19高表达的外泌体能显著增强Hep3B和HepG2细胞的增殖、迁移和侵袭能力。而这一作用可通过激活PI3K/AKT/mTOR通路实现。上述结果表明，lncRNA H19高表达的肝癌细胞以外泌体方式，增强邻近肝癌细胞的增殖、迁移和侵袭能力，促进肝癌的发生与发展。

Exosome-derived Long Non-coding RNA H19 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma

Exosomes are the cell derived small vesicles with a diameter of 30-150 nm, which contain mRNA, microRNA and long non coding RNA (lncRNA). It has been known that lncRNA H19 in exosomes plays an important role in regulating cell proliferation, migration and invasion in tumor. However, the detailed biological function of lncRNA is not well understood. In order to evaluate the effects of lncRNA H19 hepatocarcinoma cells on other tumor cells, we screened the cell lines of hepatocellular carcinoma with different lncRNA H19 expression levels. HCCLM3 cells showed high expression of lncRNA H19, while Hep3B and HepG2 cells showed low expression of lncRNA H19. The lncRNAH19 was knocked down by siRNA in HCCLM3 cells. The results showed that the expression of lncRNA H19 was significantly reduced. Both Hep3B and HepG2 cells were transfected with exosomes derived from HCCLM3 cells with high expression of lncRNA H19 or HCCLM3 cells with the lncRNA H19 knockdown. MTs, colony formation, and transwell assays were performed to investigate the behavior of Hep3B and HepG2 cells. The results showed that HCCLM3 derived exosomes could be released from cells in culture and endocytosed by the Hep3B and HepG2 cells. Compared with the control cells, the depletion of lncRNA H19 in exosomes inhibited cells proliferation, migration and invasion in Hep3B and HepG2. The data also showed that the PI3K/AKT/mTOR pathway was activated by lncRNA H19 overexpression to promote cell proliferation and migration. The above results indicated that lncRNA H19 in exosomes plays an important role in regulating cell proliferation, migration and invasion in hepatocarcinoma, and promotes the carcinogenesis and development of cancer cells.