MiR-489 suppresses multiple myeloma cells growth through inhibition of LDHA-mediated aerobic glycolysis.

Abstract

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. To investigate whether miR-489 induced MM growth inhibition via targeting to LDHA-mediated aerobic glycolysis. 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. 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. miR-489 inhibited MM tumor growth via LDHA-mediated glycolytic metabolism, suggesting potential therapeutic target ability of miR-489/LDHA for MM.