c-Myc, RMRP, and miR-34a-5p form a positive-feedback loop to regulate cell proliferation and apoptosis in multiple myeloma

Abstract Long non-coding RNA (lncRNA) component of mitochondrial RNA processing endoribonuclease (RMRP) has been demonstrated to be implicated in human cancer processes. However, the role of lncRNA RMRP in multiple myeloma (MM) remains unknown. In this paper, we proved that RMRP and c-Myc were upregulated, while miR-34a-5p was downregulated in MM cell lines and bone marrows of MM patients. High RMRP expression significantly correlated with worse disease-free survival and overall survival in MM patients. c-Myc promoted RMRP transcription by directly binding to its promoter region. Knockdown of RMRP inhibited proliferation and promoted apoptosis of OPM2 and RPMI-8226 cells. Negative correlation between RMRP, and miR-34a-5p was discovered in bone marrows of MM patients. c-Myc expression was inversely correlated with miR-34a-5p in bone marrows of MM patients. Additionally, silencing of RMRP led to a marked reduction in c-Myc expression in OPM2 and RPMI-8226 cells, and this action was obviously blocked by miR-34a-5p knockdown. Moreover, upregulation of miR-34a-5p repressed proliferation and promoted apoptosis of OPM2 and RPMI-8226 cells. However, RMRP overexpression blocked these changes triggered by miR-34a-5p mimic. Besides, RMRP knockdown repressed MM tumor growth in vivo . Conclusions, RMRP functions as a miR-34a-5p sponge to promote cell proliferation and repress cell apoptosis through upregulation of c-Myc in MM.