Zuo Wenli, Zhou Keshu, Deng Mei, Lin Quande, Yin Qingsong, Zhang Chunlei, Zhou Jian, Song Yongping
Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan, China.
Aging (Albany NY). 2020 Oct 4;12(19):18970-18981. doi: 10.18632/aging.103252.
Despite continuous improvements of AML therapy, the prognosis of AML patients remains unsatisfactory. Recently, lncRNAs have been reported to participate in the development of AML. Our data demonstrated that MMP15 and LINC00963 were upregulated and miR-608 was decreased in AML cells (THP-1, HL-60, HEL and MOLM-13) compared to HS-5 cells. RT-qPCR results showed that LINC00963 levels were higher in the serum and bone marrow of AML cases than in controls. Moreover, overexpression of LINC00963 promoted AML cell growth and EMT progression in both THP-1 and HL-60 cells. Furthermore, miR-608 levels were downregulated in the serum and bone marrow of AML cases compared with controls, and Pearson's correlation analysis indicated that LINC00963 was negatively correlated with miR-608 in the serum and bone marrow of AML samples. In addition, we demonstrated that LINC00963 sponged miR-608 expression and that MMP-15 was a target of miR-608 in AML cells. Finally, rescue experiments indicated that ectopic expression of LINC00963 accelerated cell growth and EMT development by modulating MMP-15. These data demonstrated that LINC00963 acted as an oncogene and may be a potential target for AML treatment.
尽管急性髓系白血病（AML）治疗不断改进，但AML患者的预后仍不尽人意。最近，有报道称长链非编码RNA（lncRNAs）参与了AML的发生发展。我们的数据表明，与HS-5细胞相比，AML细胞（THP-1、HL-60、HEL和MOLM-13）中基质金属蛋白酶15（MMP15）和LINC00963上调，而miR-608降低。逆转录定量聚合酶链反应（RT-qPCR）结果显示，AML病例血清和骨髓中LINC00963水平高于对照组。此外，LINC00963的过表达促进了THP-1和HL-60细胞中AML细胞的生长和上皮-间质转化（EMT）进程。此外，与对照组相比，AML病例血清和骨髓中miR-608水平下调，Pearson相关性分析表明，AML样本血清和骨髓中LINC00963与miR-608呈负相关。此外，我们证明LINC00963可吸附miR-608的表达，且基质金属蛋白酶-15（MMP-15）是AML细胞中miR-608的靶标。最后，挽救实验表明，LINC00963的异位表达通过调节MMP-15加速细胞生长和EMT进展。这些数据表明，LINC00963作为一种癌基因，可能是AML治疗的潜在靶点。
