Serum miR-30d as a novel biomarker for multiple myeloma and its antitumor role in U266 cells through the targeting of the MTDH/PI3K/Akt signaling pathway

Abstract

Multiple myeloma (MM) is a hematological tumor and is characterized by the infiltration of malignant clonal plasma cells (PCs) in bone marrow. MicroRNAs (miRNAs or miRs) have been reported to play an important role in the genesis and progression of MM. However, little is known about the clinical diagnostic value and biological functions of miR-30d in MM. In this study, to investigate the role of miR-30d in MM, we used reverse transcription-quantitative polymerase chain reaction quantitative (RT-qPCR) to detect the relative expression level of miR-30d in the serum of 81 patients with primary MM and 78 healthy donors (HDs). The biological functions of miR-30d were then assessed by CCK-8 assay, flow cytometric analysis of apoptosis and western blot (WB) analysis in U266 cells. Moreover, the confirmation of the target gene of miR-30d was conducted by luciferase reporter assay. Our results indicated that miR-30d expression was significantly downregulated in the serum of patients with primary MM compared with that of the HDs and that it was significantly associated with several clinical indicators of MM. Further cell functional analyses using the U266 cells revealed that miR-30d functions as a tumor suppressor gene in MM by inhibiting cell viability and promoting cell apoptosis. Moreover, miR-30d was confirmed to directly bind to the 3'UTR of its target gene, metadherin (MTDH) and inhibit the activation of the downstream PI3K/Akt signaling pathway. On the whole, the findings of this study indicate that the serum expression level of miR-30d is of great significance to the diagnosis and treatment monitoring of patients with MM. Moreover, miR-30d carries out its antitumor role in U266 cells through the inhibition of the activation of the PI3K/Akt signaling pathway by negatively regulating MTDH, which reveals its potential for use as a therapeutic target for MM.

Retracted Article: Long non-coding RNA PCAT1 facilitates cell growth in multiple myeloma through an MTDH-mediated AKT/β-catenin signaling pathway by sponging miR-363-3p

“…Previous reports were in agreement with our data. 26,27 These data elucidated that PCAT1 positively modulates MTDH expression to promote cell growth in MM through the AKT/b-catenin signaling pathway.…”

“…22) and has been identied as an oncogene to regulate cell behavior, 23,24 angiogenesis, 25 and chemoresistance 22 in various cancers including MM. 26,27 However, the molecular mechanisms of miR-363-3p and MTDH have barely been reported in MM. In this research, we focused mainly on the roles of PCAT1 and MTDH in MM.…”

Role of microRNAs in Diagnosis, Prognosis and Management of Multiple Myeloma

“…Serum analysis revealed a combination of up-regulated miR-34a and down-regulated let-7e could distinguish MM from control with a sensitivity and specificity of 80%, and MGUS with a sensitivity and specificity of over 90% ( Table 3 ) [ 183 ]. Other suggested markers include increased plasma miR-125b-5p, serum miR-29a, serum miR-4449, and decreased serum miR-30d and miR-203 levels [ 184 , 185 , 186 , 187 , 188 ]. In addition, the miR-125b-5p level was associated with extramedullary infiltration and was significantly higher in stage III patients compared to stage I/II patients [ 184 ].…”

Genome-wide identification of potential biomarkers in multiple myeloma using meta-analysis of mRNA and miRNA expression data

“…4 ) was also noted. The miR-30d-3p is a known prognostic biomarker for MM reported to have lower serum expression levels and tumor suppressor functions mediated through direct targeting of TP53 and MTDH/PI3K/Akt signaling pathway 59 . A recent study has reported high expression of miR-16–2-3p in serum of Bortezomib refractory MM patients 60 but its role in MM has not been investigated thoroughly.…”