Department of Gastroenterology, The Sixth Peaple's Hospital of Qingdao, Qingdao, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Sep;22(17):5490-5498. doi: 10.26355/eurrev_201809_15809.
To study the effects of chronic virus-mediated micro ribonucleic acid miR-27a on proliferation and migration capacities of liver cancer cells.
A total of 60 patients with primary liver cancer from January 2015 to December 2016 were selected as observation group, 60 patients with chronic liver disease were selected as control group, and another 60 healthy subjects who received physical examination during the same period were selected as healthy group. All patients received serum miRNA detection. The different expressions of serum miRNAs in healthy people, patients with chronic liver disease, and patients with liver cancer were analyzed. The correlations of miR-27a with growth and proliferation of liver cancer MCC-7721 cells were studied.
The levels of miR-27a and miR-664b in subjects in control group and healthy group were significantly lower than those in observation group, but the expression levels of miR-30a were statistically elevated (p<0.05). The expression of serum miR-27a in liver cancer patients with higher tumor-node-metastasis (TNM) staging (stage III-IV, number of tumors >1, tumor size >5 cm, and vascular invasion) was significantly higher than those in patients with lower TNM staging (stage I-II, number of tumors =1, tumor size ≤5 cm, and no vascular invasion) (p<0.05). At 48 h and 72 h after transfection, the proliferation of liver cancer MCC-7721 cells was significantly enhanced compared to that in non-transfection group (p<0.05). The level of miR-27a was significantly upregulated in cisplatin-resistant liver cancer A549/CDDP cells compared with that in parental A549 cells. MiR-27a regulated epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro, while modulated the in vivo response of liver cancer cells to cisplatin. Further studies identified the Raf kinase inhibitor protein (RKIP) as a direct and functional target of miR-27a. The knockdown of RKIP by RNAi showed a similar effect to ectopic miR-27a expression, whereas the over-expression of RKIP weakened the function of miR-27a in liver cancer cells.
MiR-27a participated in the proliferation and migration capacities of liver cancer cells and influenced the effect of cisplatin via targeting RKIP. The high expression of miR-27a is closely related to the malignant degree of liver cancer, which provides guidance for the diagnosis, targeted therapy, and prognostic evaluation of liver cancer.
研究慢性病毒介导的 micro ribonucleic acid miR-27a 对肝癌细胞增殖和迁移能力的影响。
选取 2015 年 1 月至 2016 年 12 月收治的原发性肝癌患者 60 例为观察组，同期慢性肝病患者 60 例为对照组，另选取同期体检健康者 60 例为健康组。所有患者均进行血清 miRNA 检测，分析健康人群、慢性肝病患者及肝癌患者血清 miRNA 的不同表达，研究 miR-27a 与肝癌 MCC-7721 细胞生长增殖的相关性。
对照组和健康组受试者的 miR-27a 和 miR-664b 水平明显低于观察组，而 miR-30a 的表达水平则明显升高（p<0.05）。肿瘤-淋巴结-转移（TNM）分期较高（III-IV 期，肿瘤数量>1，肿瘤大小>5 cm，血管侵犯）的肝癌患者血清 miR-27a 表达明显高于分期较低（I-II 期，肿瘤数量=1，肿瘤大小≤5 cm，无血管侵犯）的患者（p<0.05）。转染后 48 h 和 72 h，肝癌 MCC-7721 细胞的增殖明显高于未转染组（p<0.05）。与亲本 A549 细胞相比，顺铂耐药肝癌 A549/CDDP 细胞中 miR-27a 的水平明显上调。miR-27a 体外调节上皮-间充质转化（EMT）和顺铂耐药，同时调节肝癌细胞对顺铂的体内反应。进一步的研究确定 Raf 激酶抑制剂蛋白（RKIP）为 miR-27a 的直接和功能靶标。通过 RNAi 敲低 RKIP 显示出与外源性 miR-27a 表达相似的效果，而过表达 RKIP 则削弱了 miR-27a 在肝癌细胞中的功能。
miR-27a 参与肝癌细胞的增殖和迁移能力，并通过靶向 RKIP 影响顺铂的作用。miR-27a 的高表达与肝癌的恶性程度密切相关，为肝癌的诊断、靶向治疗和预后评估提供了指导。
