Identification of MSRA gene on chromosome 8p as a candidate metastasis suppressor for human hepatitis B virus-positive hepatocellular carcinoma.
Identification of MSRA gene on chromosome 8p as a candidate metastasis suppressor for human hepatitis B virus-positive hepatocellular carcinoma.
复制标题
鉴定 8p 号染色体上的 MSRA 基因作为人乙型肝炎病毒阳性肝细胞癌的候选转移抑制基因
DOI：
10.1186/1471-2407-7-172
复制
发表时间：
2007-09-04
期刊：
影响因子：
3.8
通讯作者：
Qin LX
中科院分区：
文献类型：
--
作者：
Lei KF;Wang YF;Zhu XQ;Lu PC;Sun BS;Jia HL;Ren N;Ye QH;Sun HC;Wang L;Tang ZY;Qin LX
背景
肝细胞癌（HCC）患者的预后仍然很差，这主要是由于转移。在我们以前的研究中，我们发现染色体8 p缺失可能与肝癌的转移有关。在这项研究中，我们的目的是确定在染色体8 p的候选转移抑制基因。
方法
构建了包含人类染色体8 p上322个基因的寡核苷酸芯片，用于分析有转移和无转移的HCC组织中基因表达谱的差异。通过实时荧光定量PCR和Western blotting方法对差异表达基因进行筛选和分析。构建各靶基因的重组表达质粒载体，转染肝癌细胞，观察其对肝癌细胞增殖和侵袭能力的影响。
结果
有转移的肝癌组织与无转移的肝癌组织相比，有16个差异表达基因（p0.01，q 16%）.在10个显著下调的肝癌转移相关基因中，甲硫氨酸亚砜还原酶A（MSRA）的p值和误报率（FDR）最低，被认为是潜在的转移抑制基因。Real-time PCR和Western blotting证实，有转移的HCC中MSRA的mRNA和蛋白表达水平均明显低于无转移的HCC（p0.001），高转移潜能的HCCLM 6细胞中MSRA的mRNA水平也明显低于其他HCC细胞系。转染重组表达质粒载体并过表达MSRA基因可明显抑制HCCLM 6细胞系的集落形成（4.33 ± 2.92 vs.9.17 ± 3.38，p = 0.008）和侵袭力（7.40 ± 1.67 vs.17.20 ± 2.59，p= 0.0001）。
结论
染色体8 p上的MSRA基因可能具有肝癌转移抑制活性。
Background
The prognosis of patients with hepatocellular carcinoma (HCC) still remains very dismal, which is mainly due to metastasis. In our previous studies, we found that chromosome 8p deletions might contribute to metastasis of HCC. In this study, we aimed to identify the candidate metastatic suppressor gene on chromosome 8p.
Methods
Oligo-nucleotide microarrays which included 322 genes on human chromosome 8p were constructed to analyze the difference in gene expression profiles between HCC tissues with and without metastasis. The leading differentially expressed genes were identified and selected for further analysis by real-time PCR and Western blotting. Recombinant expression plasmid vectors for each target gene were constructed and transfected into HCC cells and its in vitro effects on proliferation and invasion of HCC cells were also investigated.
Results
Sixteen leading differentially expressed genes were identified from the HCC tissues with metastasis compared with those without metastasis (p 0.01, q 16 %). Among of the 10 significantly down-regulated genes in HCC with metastasis, methionine sulfoxide reductase A (MSRA) had the lowest p value and false discovery rate (FDR), and was considered as a potential candidate for metastasis suppressor gene. Real-time PCR and Western blotting confirmed that the mRNA and protein expression levels of MSRA were significantly decreased in HCC with metastasis compared with those without metastasis (p 0.001), and MSRA mRNA level in HCCLM6 cells (with high metastatic potential) was also much lower than that of other HCC cell lines. Transfection of a recombinant expression plasmid vector and overexpression of MSRA gene could obviously inhibit cell colony formation (4.33 ± 2.92 vs. 9.17 ± 3.38, p = 0.008) and invasion (7.40 ± 1.67 vs. 17.20 ± 2.59, p= 0.0001) of HCCLM6 cell line.
Conclusion
MSRA gene on chromosome 8p might possess metastasis suppressor activity in HCC.
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宿主遗传学和肿瘤转移。
影响因子：
8.8
作者：
Hunter, K W
通讯作者：
Hunter, K W
影响因子：
4
作者：
Mitsunobu, M;Toyosaka, A;Nakao, N
通讯作者：
Nakao, N
影响因子：
4.7
作者：
Muscheck, M;Abol-Enein, H;Waldman, FM
通讯作者：
Waldman, FM
影响因子：
11.2
作者：
Nonaka, D;Fabbri, A;Sozzi, G
通讯作者：
Sozzi, G
DOI：
10.1073/pnas.0403532101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Kantorow, M;Hawse, JR;Hejtmancik, JF
通讯作者：
Hejtmancik, JF