白藜芦醇苷通过抑制长链非编码RNA HULC表达抑制肝癌SMMC-7721和HepG2细胞的增殖和侵袭

原发性肝癌是临床上最常见的恶性肿瘤之一，目前仍在寻找有效的治疗手段。我们之前的研究证实白藜芦醇苷能够抑制肝癌细胞的增殖和侵袭，但其具体的分子生物学机制仍不清楚。本文主要探讨白藜芦醇苷调控肝癌细胞系SMMC-7721和HepG2肝癌细胞系增殖能力的分子生物学机制。首先，我们构建大鼠原发性肝癌模型，发现模型组肝组织中长链非编码RNA HULC的表达较正常组明显升高；同时检测白藜芦醇苷预防组（分为低剂量组，中剂量组和高剂量组）肝组织中肝癌细胞中出现异常的高表达(HULC)的表达情况。结果显示，在中、高剂量组中HULC的表达明显降低。在体外实验中，SMMC7721和HepG2中HULC的表达明显较正常肝组织显著增高，然而白藜芦醇苷高剂量组中HULC的表达发生明显降低，同时在SMMC7721和HepG2中加入白藜芦醇苷后，高剂量组中细胞增殖能力明显下降。为了进一步探究HULC在白藜芦醇苷预防肝癌中的功能，我们构建了HULC过表达质粒以及针对HULC的siRNA片段，并验证了过表达和敲低的效率。在使用高剂量白藜芦醇苷处理SMMC7721和HepG2的同时，过表达HULC能够逆转白藜芦醇苷引起的对细胞增殖的抑制，然而敲低HULC则能够更加有效地降低白藜芦醇苷对细胞增殖的抑制效果。这提示我们白藜芦醇苷能够可能通过调控HULC的表达抑制肝癌细胞的增殖和侵袭，二者具有协同作用。本文结果为预防原发性肝癌提供了新的理论依据但其临床疗效还需要进一步验证。

Polydatin Suppresses Expression of Long-noncoding RNA HULC and Inhibits the Proliferation and Invasion of SMMC-7721 and HepG2 Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, which demands of effective clinical treatments. Previous study has shown that polydatin inhibited the proliferation and invasion of HCC cells, however, the molecular mechanism is unclear. In a HCC rat model, we found that the HULC (highly up-regulated in liver cancer) expression was significantly upregulated. Polydatin suppressed the HULC expression in vivo. Polydatin was able to inhibit the proliferation of SMMC7721 and HepG2 cells and downregulate the expression of HULC. In addition, from experiments with gain of function and loss of function of HULC, the result showed that polydatin inhibited the proliferation rate of SMMC7721 and HepG2 cells. We hypothesized that polydatin inhibited the proliferation of HCC via a HULC-related mechanism.