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KMID : 0381120200420030291
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Genes and Genomics
2020 Volume.42 No. 3 p.291 ~ p.297
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miR-489 suppresses multiple myeloma cells growth through inhibition of LDHA-mediated aerobic glycolysis
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Wu Han
Wang Xiuhong
Wu Tingting
Yang Su
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Abstract
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Background: Dysregulation of miR-489 in human tumors has been widely reported. Lactate dehydrogenase isoform A (LDHA)-mediated aerobic glycolysis participates in proliferation of multiple myeloma (MM) cells.
Objective: To investigate whether miR-489 induced MM growth inhibition via targeting to LDHA-mediated aerobic glycolysis.
Methods: Expression of miR-489 in representative MM cell lines was determined via qRT-PCR (quantitative real-time polymerase chain reaction). MTT (3-(4, 5-di methyl thiazol-2-yl)-2, 5-di phenyl tetrazolium bromide) and colony formation assays were utilized to detect cell viability and proliferation. Effect of miR-489 on aerobic glycolysis was detected via glucose uptake, lactate and ATP production. Binding ability between miR-489 and LDHA was conducted via luciferase activity assay.
Results: MiR-489 was down-regulated in representative MM cell lines. Gain-of functional assays indicated that over-expression of miR-489 decreased cell viability and inhibited cell proliferation of MM cells. Moreover, miR-489 inhibited aerobic glycolysis via decrease of glucose uptake, lactate and ATP production. LDHA was identified as target of miR-489, suggesting a negative correlation between miR-489 and LDHA in MM cells. Mechanically, the inhibition ability of miR-489 on proliferation of MM cells was through inhibition of LDHA-mediated aerobic glycolysis.
Conclusions: miR-489 inhibited MM tumor growth via LDHA-mediated glycolytic metabolism, suggesting potential therapeutic target ability of miR-489/LDHA for MM.
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KEYWORD
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miR-489, Aerobic glycolysis, Proliferation, LDHA, Multiple myeloma
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