LRRC75A-AS1 targets miR-199b-5p/PDCD4 axis to repress multiple myeloma

Multiple functions of miR-199b-5p in diseases have been demonstrated by existing studies. However, never has the correlation between miR-199b-5p and multiple myeloma (MM) been established.

qRT-PCR analyzed RNA expression and western blot measured protein expression. Cell proliferation ability was tested via colony formation and EdU assays, and apoptosis was determined via TUNEL, flow cytometry and detection of apoptosis-related proteins. Position of LRRC75A antisense RNA 1 (LRRC75A-AS1) was recognized by FISH assay. RIP, RNA pull-down and luciferase reporter experiments explored the molecular interplay.

GEO (Gene Expression Omnibus) data revealed miR-199b-5p upregulation in MM specimens, and qRT-PCR data verified miR-199b-5p upregulation in MM cells. Inhibiting miR-199b-5p markedly impeded MM cell proliferation and stimulated apoptosis. Moreover, we demonstrated the mechanism that miR-199b-5p was decoyed by LRRC75A-AS1 and miR-199b-5p targeted programmed cell death 4 (PDCD4) to repress its expression. Further, LRRC75A-AS1 was verified to repress proliferation and prompt apoptosis in a PDCD4-dependent way in MM cells.

Our data displayed that miR-199b-5p was sequestered by LRRC75A-AS1 so that PDCD4 was released to repress MM, implying the targeting miR-199b-5p as a novel thought for improving MM therapy.