HCP5 作为 miR-1291 的海绵，通过增加 PIK3R5 表达促进 AML 细胞增殖并抑制细胞凋亡。

HCP5, as the sponge of miR-1291, facilitates AML cell proliferation and restrains apoptosis via increasing PIK3R5 expression.

机构信息

Department of Hematology, Zibo Central Hospital, No. 54 Gongqingtuan West Road, Zhangdian District, Zibo, 255000, Shandong, People's Republic of China.

Department of Nursing, Zibo Central Hospital, Zibo, 255000, Shandong, People's Republic of China.

出版信息

Hum Genomics. 2021 Jun 29;15(1):38. doi: 10.1186/s40246-021-00340-5.

BACKGROUND

Acute myeloid leukemia (AML) is recognized as a hematological neoplasm with heterogenetic cytology and short-term outcome. HCP5 has been proven to be related with the pathogenesis of AML. However, the underlying mechanism of HCP5 in AML remains unclear.

METHODS

Clinical profiles of AML patients were downloaded from TCGA and GTEx databases. LncBase and TargetScan online tools were utilized to predict potential targets, and dual-luciferase reporter assay was performed to verify the association between miR-1291 and HCP5 or PIK3R5. Cell Counting Kit 8 and flow cytometry tests were implemented to evaluate the effects of HCP5/miR-1291/PIK3R5 axis in AML cells. Quantitative RT-PCR and Western blot were conducted to detect the expression levels of genes.

RESULTS

HCP5 and PIK3R5 were significantly increased in AML tissue samples compared with healthy controls. HCP5 facilitated AML cells viability and inhibited apoptosis. There was a positive relationship between HCP5 and PIK3R5, but miR-1291 negatively regulated PIK3R5. Overexpression of PIK3R5 enhanced the promoting effect of HCP5 in the development of AML, while weakened the suppression of miR-1291 to AML progression.

CONCLUSION

Our findings manifested that HCP5 was remarkably upregulated in AML and upregulated HCP5 promoted the malignant behaviors of AML cells by mediating miR-1291/PIK3R5 axis, which would provide a new insight for the treatment of AML.

背景

急性髓系白血病（AML）被认为是一种具有异质性细胞学和短期预后的血液系统恶性肿瘤。HCP5 已被证明与 AML 的发病机制有关。然而，HCP5 在 AML 中的潜在机制尚不清楚。

方法

从 TCGA 和 GTEx 数据库中下载 AML 患者的临床资料。利用 LncBase 和 TargetScan 在线工具预测潜在靶点，并通过双荧光素酶报告基因实验验证 miR-1291 与 HCP5 或 PIK3R5 的关系。通过细胞计数试剂盒 8 和流式细胞术实验评估 HCP5/miR-1291/PIK3R5 轴在 AML 细胞中的作用。采用定量 RT-PCR 和 Western blot 检测基因的表达水平。

结果

与健康对照组相比，AML 组织样本中 HCP5 和 PIK3R5 的表达明显增加。HCP5 促进 AML 细胞的活力并抑制细胞凋亡。HCP5 与 PIK3R5 呈正相关，而 miR-1291 负调控 PIK3R5。过表达 PIK3R5 增强了 HCP5 在 AML 发生发展中的促进作用，而减弱了 miR-1291 对 AML 进展的抑制作用。