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长链非编码 RNA VPS9D1-AS1 通过 miR-491-5p 和 miR-214-3p 逃避调节 GPX1 表达促进急性淋巴细胞白血病细胞增殖。

LncRNA VPS9D1-AS1 promotes cell proliferation in acute lymphoblastic leukemia through modulating GPX1 expression by miR-491-5p and miR-214-3p evasion.

机构信息

Department of Hematology, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.

出版信息

Biosci Rep. 2020 Oct 30;40(10). doi: 10.1042/BSR20193461.

Abstract

Alterations in messenger RNAs (mRNAs) of protein-coding genes can influence the malignant behaviors of acute lymphoblastic leukemia (ALL) cells. According to the prediction from The Cancer Genome Atlas (TCGA) database, we discovered that glutathione peroxidase 1 (GPX1) was up-regulated in acute myeloid leukemia (LAML) tissues, which pushed us to explore the feasible role and its related modulatory mechanism of GPX1 in ALL. In this research, we first proved the high expression of GPX1 in ALL cells compared with normal cells. Functional assays further revealed that the proliferation was obstructed and the apoptosis was facilitated in ALL cells with silenced GPX1. Then, both miR-491-5p and miR-214-3p that were down-regulated in ALL cells were affirmed to target GPX1. Subsequently, VPS9D1 antisense RNA 1 (VPS9D1-AS1) was recognized as the upstream regulator of miR-491-5p-miR-214-3p/GPX1 axis in a competing endogenous RNA (ceRNA) model. Importantly, we proved that VPS9D1-AS1 served as a tumor promoter in ALL through elevating GPX1. In conclusion, VPS9D1-AS1 contributed to ALL cell proliferation through miR-491-5p-miR-214-3p/GPX1 axis, hinting an optional choice for the treatment of ALL.

摘要

信使 RNA(mRNA)的改变可影响急性淋巴细胞白血病(ALL)细胞的恶性行为。根据癌症基因组图谱(TCGA)数据库的预测,我们发现谷胱甘肽过氧化物酶 1(GPX1)在急性髓系白血病(LAML)组织中上调,这促使我们探索 GPX1 在 ALL 中可行的作用及其相关调节机制。在这项研究中,我们首先证明了 ALL 细胞中 GPX1 的高表达与正常细胞相比。功能测定进一步表明,沉默 GPX1 可阻碍 ALL 细胞的增殖并促进其凋亡。然后,我们证实了 miR-491-5p 和 miR-214-3p 在 ALL 细胞中下调,可靶向 GPX1。随后,在竞争性内源性 RNA(ceRNA)模型中,我们识别出 VPS9D1 反义 RNA 1(VPS9D1-AS1)是 miR-491-5p-miR-214-3p/GPX1 轴的上游调节因子。重要的是,我们通过提高 GPX1 证明了 VPS9D1-AS1 在 ALL 中作为肿瘤促进因子的作用。总之,VPS9D1-AS1 通过 miR-491-5p-miR-214-3p/GPX1 轴促进 ALL 细胞增殖,提示了治疗 ALL 的一种可选选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a8d/7536331/ced1583efada/bsr-40-bsr20193461-g1.jpg

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