MXRA7基因对急性B淋巴细胞白血病REH细胞功能的影响

Effect of MXRA7 on the Biological Functions of Acute B Lymphoblastic Leukemia Cell Line REH

目的:发掘基质重塑相关7(MXRA7)基因与急性B淋巴细胞白血病(B-ALL)的关联,并探究MXRA7对B-ALL细胞系REH细胞生物学功能的影响。方法:通过Blood Spot数据库检索并分析MXRA7在血液疾病中的表达情况。应用Real-time q PCR检测B-ALL细胞株697、REH细胞中MXRA7的表达水平;采用慢病毒介导的sh RNA干扰技术敲低REH细胞中MXRA7的表达,通过CCK-8实验检测细胞增殖、PI染色检测细胞周期、Annexin V和7-AAD流式染色检测细胞凋亡、Western blot检测凋亡通路相关蛋白的表达。结果:数据库分析显示MXRA7在B-ALL患者中高表达,Real-time q PCR结果表明MXRA7在细胞株697、REH细胞中也存在较高表达;敲低MXRA7后REH细胞增殖能力降低,且细胞G_(0)/G_(1)期比例升高;阿糖胞苷处理后,敲低MXRA7的REH细胞凋亡比例升高,且Caspase-3及Caspase-9活化水平升高。结论:敲低MXRA7可通过抑制REH细胞增殖、增加REH细胞对阿糖胞苷的敏感性等来减弱REH细胞的恶性程度。这些结果提示MXRA7可能成为B-ALL治疗的潜在靶点。

Objective: To discover the relationship between matrix remodeling associated 7(MXRA7) and acute B lymphoblastic leukemia(B-ALL), and explore the effect of MXRA7 on the biological functions of B-ALL cell line REH. Methods: The expression of MXRA7 in blood diseases was searched and analyzed through Blood Spot database. Realtime q PCR was used to detect the expression level of MXRA7 in B-ALL cell line 697 and REH cells. Lentivirus-mediated sh RNA interference technology was utilized to knock down the expression of MXRA7 in REH cells. The effects of MXRA7 on the biological functions of REH cells were studied by in vitro experiments. Cell proliferation was detected by CCK-8 assay, cell cycle was detected by PI staining, cell apoptosis was detected by Annexin V and 7-AAD staining, and the expression of apoptosis pathway related proteins was detected by Western blot. Results: Database analysis showed that MXRA7 was highly expressed in B-ALL patients, and real-time q PCR results showed that MXRA7 was also highly expressed in cell lines 697 and REH cells. Knockdown of MXRA7 in REH cells inhibited the cell proliferation and increased the percentage of G_(0)/G_(1) phase cells. After treatment with cytarabine, the apoptotic ratio was increased in MXRA7-impaired REH cells, and the activation of caspase-3 and caspase-9 were also increased. Conclusion: Knockdown of MXRA7 can reduce the malignancy of REH cells by inhibiting the cell proliferation and increasing the sensitivity of REH cells to cytarabine. These results indicate MXRA7 may be as a novel target for the treatment of B-ALL, and the potential usefulness of MXRA7 in B-ALL deserves further investigation.