Lncrna Rmrp Regulate Mitochondrial Function in Relapsed and Refractory Acute Myeloid Leukemia

Background: The prognosis of relapsed and refractory acute myeloid leukemia (R/R AML) is extremely poor, primarily due to the development of chemotherapy resistance during the treatment, which leads to its relapse and refractory disease. Extensive studies have established that various dysfunctions in the mitochondria of AML cells play a significant role in promoting chemotherapy resistance and the recurrence of the disease. In our previous investigation, we successfully demonstrated the substantial enrichment of the long non-coding RNA (lncRNA) RMRP in the mitochondria. However, the specific function of RMRP in the mitochondria of R/R AML remains unexplored. The objective of this project is to uncover the function of RMRP in R/R AML mitochondria, aiming to provide innovative insights and a theoretical foundation for surmounting chemotherapy resistance in R/R AML. Methods: In order to investigate the factors that play a crucial role in R/R AML, we employed mass spectrometry (MS) to conduct a screening of factors associated with AML chemoresistance. We utilized quantitative real-time polymerase chain reaction (RT-qPCR) to assess the expression of lncRNA RMRP in both newly diagnosed AML (ND AML) and R/R AML patients. Furthermore, we knocked down the RMRP expression level by transfection with siRNA-NC and siRNA-RMRP. Additionally, we analyzed the correlation between lncRNA RMRP and mitochondria. To explore the involvement of lncRNA RMRP in regulating mitochondrial function in R/R AML, we performed mitochondrial oxidative phosphorylation metabolic function assays subsequent to the inhibition of lncRNA RMRP. Moreover, Western blot analysis was employed to evaluate the relative protein expression levels in AML cell lines. Results: We enrolled 23 AML patients (ND AML, n=12; R/R AML, n=11), and the result of MS shows that R/R AML group expressed higher level of mitochondria related protein. The qPCR results showed that R/R AML had higher expression level of RMRP ( P