MiRNA expression profiles reveal the involvement of miR-26a, miR-5481 and miR-34a in hepatocellular carcinoma progression through regulation of ST3GAL5
MiRNA expression profiles reveal the involvement of miR-26a, miR-5481 and miR-34a in hepatocellular carcinoma progression through regulation of ST3GAL5
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DOI：
10.1038/labinvest.2017.12
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发表时间：
2017-05-01
影响因子：
5
通讯作者：
Jia, Li
中科院分区：
文献类型：
--
作者：
Cai, Hongjiao;Zhou, Huimin;Jia, Li
microRNAs（miRNAs）通过翻译抑制作用靶向特定基因，在生理和病理过程中发挥重要作用。与转移相关的miRNAs的鉴定使我们能够更好地了解癌症的发展。在本研究中，我们研究了miRNA表达谱的高度侵袭性的人肝癌细胞系MHCC 97-H和MHCC 97-L的低转移潜力，使用miRNA微阵列。通过实时荧光定量PCR，我们证实了miRNA实验的结果。在MHCC 97-H和MHCC 97-L细胞中发现了13个差异表达的miRNAs;在临床样本中发现了相同的结果。通过生物信息学分析和荧光素酶报告基因分析，我们发现唾液酸转移酶基因ST 3GAL 5是miR-26 a、miR-5481和miR-34 a的直接靶基因。miR-26 a、miR-5481或miR-34 a在MHCC 97-H或MHCC 97-L细胞中的工程表达可显著改变其体外和体内实验中的恶性行为和致瘤性。ST 3GAL 5的调控表达也导致MHCC 97-H和MHCC 97-L细胞转移潜能的改变，与上述三种miRNA的作用一致。总之，我们的数据表明，这些miRNAs的水平可用作评估肝细胞癌进展的生物学标志物。miR-26 a、miR-5481和miR-34 a作为肿瘤抑制因子，可能通过调节ST 3GAL 5发挥其作用。
MicroRNAs (miRNAs) have key roles in comprehensive physiological and pathological processes by targeting specific genes through translational repression. Identification of miRNAs related to metastasis enables us to obtain better insight into cancer development. In the current study, we investigated the miRNA expressional profiles in the highly invasive human hepatocellular carcinoma cell line MHCC97-H and MHCC97-L with lower metastatic potential using miRNA microarrays. By quantitative real-time PCR, we confirmed the results of miRNA experiments. Thirteen differentially expressed miRNAs were identified between MHCC97-H and MHCC97-L cells; and the same results were found in clinical samples. Using bioinformatic analysis and luciferase reporter assay, we found that ST3GAL5, a sialyltransferase gene, was the direct target of miR-26a, miR-5481 and miR-34a. Engineered expression of miR-26a, miR-5481 or miR-34a in MHCC97-H or MHCC97-L cells could significantly change their malignant behaviors and oncogenicity in in vitro and in vivo assays. Manipulated expression of ST3GAL5 also led to the alteration of the metastatic potential of MHCC97-H and MHCC97-L cells, in agreement with the effects of above three miRNAs. Altogether, our data indicate that the levels of these miRNAs may be used as biological markers for evaluating hepatocellular carcinoma progression. miR-26a, miR-5481 and miR-34a, acting as tumor suppressors, may exert their effects by regulating ST3GAL5.