缺氧诱导因子1 α在骨髓增生异常综合征患者中的表达意义及潜在机制

2019年3月，广西医科大学**附属医院病理科；广西医科大学**附属医院肿瘤内科(Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China；Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China) Zhi‐gang Peng老师研究团队在《Cancer Medicine》上发表论文：

“Expression significance and potential mechanism of hypoxia-inducible factor 1 alpha in patients with myelodysplastic syndromes”

“缺氧诱导因子1 α在骨髓增生异常综合征患者中的表达意义及潜在机制”

Abstract：

Objective

To investigate the expression level and potential mechanism of hypoxia-inducible factor 1 alpha (HIF-1α) in patients with myelodysplastic syndromes (MDS).

Methods

Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF-1α in paraffin-embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF-1α and clinical parameters were examined. To further investigate the significance of HIF-1α expression in MDS patients, the researchers not only extracted the data about HIF-1α expression from MDS-related microarrays but also analyzed the correlation between the level of HIF-1α expression and MDS. The microRNA (miRNA) targeting HIF-1α was predicted and verified with a dual luciferase experiment.

Results

Immunohistochemistry revealed that the positive expression rate of HIF-1α in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P < .05), which indicated that HIF-1α was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF-1α in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF-1α expression was considerably higher in MDS patients than in the controls (P < .05). It was predicted that miR-93-5p had a site for binding with HIF-1α, and a dual luciferase experiment confirmed that miR-93-5p could bind with HIF-1α.

Conclusion

The upregulated expression of HIF-1α was examined in the myeloid tissues of MDS patients. The presence of HIF-1α (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR-93-5p could bind to HIF-1α by targeting, showing its potential to be the target of HIF-1α in MDS.

摘要：

目的

探讨缺氧诱导因子1α (HIF-1α)在骨髓增生异常综合征(MDS)患者中的表达水平及其潜在机制。

方法

免疫组织化学(IHC)技术检测了82例MDS患者和33例对照(淋巴瘤未侵袭髓样组织)石蜡包埋髓样组织中HIF-1α的蛋白表达。此外，研究人员还研究了HIF-1α蛋白表达与临床参数之间的关系。为了进一步探讨HIF-1α表达在MDS患者中的意义，研究人员不仅从MDS相关芯片中提取了HIF-1α表达数据，还分析了HIF-1α表达水平与MDS的相关性。通过双荧光素酶实验对靶向HIF-1α的microRNA (miRNA)进行了预测和验证。

结果

免疫组化结果显示HIF-1α在MDS患者骨髓中的阳性表达率为90.24%。这一比例显著高于对照组(72.73%)，差异有统计学意义(P < 0.05)，说明MDS患者髓系组织中HIF-1α表达上调。对于GSE2779、GSE18366、GSE41130和GSE61853微阵列，MDS患者中HIF-1α的平均表达高于对照组。特别是对于GSE18366芯片，HIF-1α在MDS患者中的表达明显高于对照组(P < 0.05)。预测miR-93-5p具有与HIF-1α结合的位点，双荧光素酶实验证实miR-93-5p能够与HIF-1α结合。

结论

HIF-1α在MDS患者骨髓组织中表达上调。HIF-1α(+)的存在提示患者预后不佳，有助于MDS的诊断。此外，miR-93-5p可以通过靶向与HIF-1α结合，显示其在MDS中可能成为HIF-1α的靶标。

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