miR-106b promotes cancer progression in hepatitis B virusassociated hepatocellular carcinoma

AIM: To investigate the effect of mi R-106 b on tumor progression in hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC).METHODS: A total of 120 patients who underwent liver resection for HCC at National Cheng Kung University Hospital were enrolled in the present study. Micro RNA(mi RNA) array was first used to screen the mi RNA expression profiles in HCC patients. The clinical records were retrospectively analyzed, and correlations with the mi RNA expression profiles were evaluated. The m RNA expression levels of the mi R-106b-25 cluster(mi R-106 b, mi R-93 and mi R-25), and MCM7 in tumor and non-tumor samples were quantitated using quantitative real-time reverse transcription-polymerase chain reaction(q-RT-PCR) analysis, and correlations in the levels of mi R-106 b, mi R-93 and mi R-25 expression were calculated. Kaplan-Meier overall and diseasefree survival rates of HBV-associated HCC patients were analyzed using the log-rank test based on mi R-106 b expression. The comparison of the mi R-106 b expression levels in patients with different clinical outcomes was analyzed using Mann-Whitney U tests. Furthermore, a hepatitis B virus X protein(HBx) expression plasmid was transfected into Huh7 and Hep 3B cells. The expression levels of the mi R-106b-25 cluster and MCM7 in HBx-expressing Huh7 and Hep 3B cells were detected using q-RT-PCR. RESULTS: mi RNA array screening showed that mi R-106 b and its cluster, mi R-93 and mi R-25 were upregulated in HCC patients(P < 0.01). The value of mi R-106 b expression in HBV-associated HCC patients was significantly higher than that in HCV-(P < 0.05) or non-B/non-C-(P < 0.001) associated HCC patients. The expression of the mi R-106b-25 cluster was significantly higher in tumor tissue(P < 0.001) and associated with the host gene, MCM7, in clinical specimens from HBVassociated HCC patients. Furthermore, the expression levels of mi R-106 b, mi R-93 and mi R-25 were positively correlated in HBV-associated HCC tissues(mi R-106 vs mi R-93, r = 0.75; mi R-93 vs mi R-25, r = 0.69; mi R-106 b vs mi R-25, r = 0.33). The overall and diseasefree survival curves showed that high-mi R-106 b expression was correlated with the poor prognosis of HBV-associated HCC. HCC differentiation was significantly correlated with mi R-106 b expression(P < 0.05). Lower mi R-106 b expression levels resulted in the well differentiation of HCC. Moreover, the expression of the mi R106b-25 cluster and MCM7 was up-regulated in Huh7 and Hep 3B cells after transfection with the HBx expression plasmid.CONCLUSION: The data obtained in the present study suggests that HBx enhances mi R-106 b transcription to promote tumor progression in HBV-associated HCC.

miR-106b-93-25簇对子宫内膜癌细胞的调控作用研究

目的:检测mi R-106b-93-25基因簇对子宫内膜癌细胞增殖及凋亡的影响,并探讨其机制。方法:q RT-PCR检测临床子宫内膜癌标本及癌旁正常组织中mi R-106b、mi R-93和mi R-25及其宿主基因MCM7的表达情况。将micro RNA及其拮抗剂转染ECC-1细胞后,MTT实验检测ECC-1细胞增殖情况,流式细胞术检测ECC-1细胞周期及细胞凋亡情况。荧光素酶报告系统验证mi R-106b和mi R-25分别直接调控p21和Bim。结果:临床标本子宫内膜癌组织与癌旁正常组织相比mi R-106b-93-25簇及其宿主基因MCM7的表达明显增高。mi R-106b-93-25簇能够促进ECC-1细胞增殖,减少凋亡。转染mi R-106b和mi R-93的细胞出现明显的S期阻滞,过表达mi R-25的细胞凋亡明显减少。mi R-106b-93-25簇通过抑制靶基因p21和Bim的表达,引起促增殖、抗凋亡作用。结论:mi R-106b-93-25簇能够促进子宫内膜癌细胞增殖,抑制凋亡,并使细胞发生S期阻滞。mi R-106b-93-25簇在子宫内膜癌的发生与发展中具有重要的作用。

miR-106b的免疫调节及其与自噬和凋亡关系的研究进展

micro RNAs（mi RNAs）是一类长度为21~25个核苷酸的内源性非编码小RNAs,在转录后水平上负向调控基因的表达。micro RNA-106b（mi R-106b）作为mi RNAs的一员,其免疫调节功能可通过影响细胞因子和转录因子的表达和TGF-β信号通路来实现。此外,mi R-106b还影响细胞的自噬和凋亡途径。现就近年来mi R-106b的研究进展作一综述。