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.
Highlights
Acute lymphoblastic leukemia (ALL) is defined as a hematologic malignancy that originated from the precursors of the lymphoid lineage, and it is one of the most frequent cancers happening in the youth, especially children [1,2,3]
Up-regulated miR-186-5p inhibits cell proliferation, metastasis and epithelial-to-mesenchymal transition (EMT) in colorectal cancer via targeting zinc finger E-box binding homeobox 1 (ZEB1) [6]; miR-612 represses stem cell-like property in hepatocellular carcinoma by controlling Sp1/Nanog pathway [7]; miR-378 enhances cell survival, tumor growth and angiogenesis through targeting SuFu and Fus-1 [8]; miR-375-HOXB3-CDCA3/DNMT3B regulatory loop makes a contribution to leukemogenesis in acute myeloid leukemia (LAML) [9]
glutathione peroxidase 1 (GPX1) was predicted to be highly expressed in LAML tissues by The Cancer Genome Atlas (TCGA) website (Figure 1A), we wondered whether GPX1 played a role in ALL. Quantitative real-time PCR (qRT-PCR) and Western blot analyses demonstrated that GPX1 messenger RNA (mRNA) and protein expression was distinctly up-regulated in ALL cells compared with normal peripheral blood mononuclear cell (PBMC) (Figure 1B and Supplementary Figure S1A)
Summary
Acute lymphoblastic leukemia (ALL) is defined as a hematologic malignancy that originated from the precursors of the lymphoid lineage, and it is one of the most frequent cancers happening in the youth, especially children [1,2,3]. MiRs are reported to exert diverse functions in cancer by affecting gene expression at post-transcriptional level [4,5]. Up-regulated miR-186-5p inhibits cell proliferation, metastasis and epithelial-to-mesenchymal transition (EMT) in colorectal cancer via targeting ZEB1 [6]; miR-612 represses stem cell-like property in hepatocellular carcinoma by controlling Sp1/Nanog pathway [7]; miR-378 enhances cell survival, tumor growth and angiogenesis through targeting SuFu and Fus-1 [8]; miR-375-HOXB3-CDCA3/DNMT3B regulatory loop makes a contribution to leukemogenesis in acute myeloid leukemia (LAML) [9]. MiR-491-5p suppresses cell proliferation and invasion via inhibition of IGF2BP1 in non-small cell lung cancer [13]. MiR-491-5p restrains cell proliferative, invasive and migratory abilities via targeting JMJD2B in gastric cancer [14]. Increased miR-214-3p enhances the cisplatin-sensitivity of License 4.0 (CC BY)
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