Han Wu1, Xiuhong Wang2, Tingting Wu2, Su Yang2. 1. Department of Clinical Laboratory Medicine, Sir Run Run Shaw Hospital Xiasha Campus, Zhejiang University School of Medicine, 368 Xiasha Road, Jianggan District, Hangzhou, 310018, Zhejiang, China. 3684203wuhan@zju.edu.cn. 2. Department of Clinical Laboratory Medicine, Sir Run Run Shaw Hospital Xiasha Campus, Zhejiang University School of Medicine, 368 Xiasha Road, Jianggan District, Hangzhou, 310018, Zhejiang, China.
Abstract
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.
BACKGROUND: Dysregulation of miR-489 in humantumors 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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