Cancer-Related Micro-RNAs May Serve as MM Bone Disease Biomarkers

Two cancer-related micro-RNAs could serve as prognostic biomarkers for multiple myeloma bone disease as lower levels were associated with lower overall survival rates, investigators concluded.

Among the several cancer-related micro-RNAs (miRNAs) found to have an association with multiple myeloma bone disease (MMBD), quantities of miR-16-5p and miR-155-5p, 2, appear to be significantly lower in plasma cells of patients with MM compared with patients with smoldering MM (sMM), according to a recent study.

Results of the quantitative investigational study searching for MM biomarkers, published in the International Journal of Molecular Sciences, mark the first time that miR-15a-5p, miR-16-5p, miR-222- 3p, and miR-125b-5p have been shown to be associated with MMBD.

“We provide evidence that miR-16-5p and miR-155-5p merit further investigation as diagnostic biomarkers, able to discriminate between MM and sMM,” wrote the investigators.

MM occurs in 1.0% to 1.8% of all malignancies and is the second most common hematological malignancy. The disease is characterized by end-organ damage, while the main clinical manifestations include hypercalcemia, anemia, renal impairment, and bone disease. The pathogenesis of MM is complex and the exact mechanisms causing progression are unknown.

In the bone marrow microenvironment, exosomes carrying miRNAs, small non-coding RNA molecules that dictate gene expression, play a critical role in cell-to-cell communication. miRNAs can regulate a number of biological functions and deregulation can lead to malignant diseases. This fact suggests they could play a role in MM by regulating the expression of oxogenes, tumor suppressor genes, and the bone marrow microenvironment in addition to potential disease progression, drug resistance, and bone destruction.

The investigators collected bone marrow samples from 76 patients who were newly diagnosed with MM at the Department of Clinical Therapeutics at the Alexandria General Hospital in Athens, Greece. The median age of the patients was 68 years, 57.9% were men, and 75 patients were receiving an MM therapy. Moreover, 21 patients underwent autologous stem cell transplantation following high-dose melphalan and 55 patients were ineligible for a bone marrow transplant.

Optimized quantitative polymerase-chain reaction assays were developed for the quantification of each miRNA sample. CD138+ plasma cells were selected from the bone marrow samples and total RNA was extracted and polyadenylated in vitro . The investigators also conducted a functional in silico analysis of the miRNAs.

Results from the Mann-Whitney U test found a statistically significant reduction in the levels of miR-16-5p and miR-155-5p in the CD138+ plasma cells of patients with MM (P = .036) in comparison with patients with sMM (P = .045). For miR-155-5p, a mean (SD) of 366.0 (167.6) relative quantification units (RQU) was observed in the CD138+ cells in patients with MM compared with 1285.7 (539.8) RQU in the cells from patients with sMM.

Additionally, lower levels of miR-15a-5p (P = .037), miR-16-5p (P = .035), and miR-222-3p (P = .037) were detected in the CD138+ plasma cells derived from patients with MM with osteolytic bone lesions compared with patients without lesions.

In reference to miR-15a-5p, a mean (SD) of 7.71 (3.25) RQU was observed in patients with osteolytic lesions compared with 29.93 (12.66) RQU in patients without the lesions. In patients with bone disease who presented with skeletal-related events, miR-125b-5p was found to be overexpressed in their CD138+ plasma cells.

The results also showed that miR-223-3p could offer favorable prognostic value in MM as lower levels of miR-223-3p were associated with significantly worse overall survival in patients with MM.

The small cohort size and short follow-up times were listed as study limitations. However, the investigators noted that their cohort was representative of the general MM population.


Papanota A, Karousi P, Kontos CK, et al. A cancer-related microRNA signature shows biomarker utility in multiple myeloma. Int J Mol Sci. 2021;22(23):12144. doi:10.3390/ijms222313144

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