How circ_0001821 Predicts Survival and Fuels Disease Progression
Multiple myeloma (MM), a cancer of plasma cells in the bone marrow, disrupts blood cell production, damages bones, and compromises immunity. Despite treatment advances, relapse remains common, creating an urgent need for better diagnostic tools and targeted therapies.
Enter circular RNAs (circRNAs)—unusual, stable RNA molecules forming closed loops. Once overlooked as cellular "glitches," they're now recognized as critical disease regulators. Among them, circ_0001821 has emerged as a key player in MM, predicting aggressive disease and fueling cancer growth. This article explores how this tiny ring-shaped RNA molecule is reshaping our approach to myeloma.
circ_0001821 is transforming our understanding of multiple myeloma progression and offering new avenues for diagnosis and treatment.
Unlike linear RNAs with distinct start and end points, circRNAs form covalently closed loops through "back-splicing." This structure grants exceptional stability—resisting degradation by RNA-cleaving enzymes—and allows persistence in tissues, blood, and even exosomes (tiny communication bubbles cells release) 2 6 .
CircRNAs act as master regulators:
A landmark 2021 study published in Hematology 1 5 provided the first comprehensive evidence of circ_0001821's role in MM.
| Clinical Parameter | Association | Implication |
|---|---|---|
| Low Hemoglobin | Strong Positive (p<0.01) | Worsened anemia due to marrow infiltration |
| High β2-Microglobulin | Strong Positive (p<0.01) | Indicates high tumor burden & poor prognosis |
| Bone Lesions | Strong Positive (p<0.01) | Linked to enhanced osteoclast activity |
| High Serum Globulin | Strong Positive (p<0.01) | Reflects elevated monoclonal protein (M-spike) |
Prognostic Power: High circ_0001821 independently predicted shorter survival (HR=3.71), making it a stronger mortality signal than many conventional markers 1 .
This proved circ_0001821 isn't just a bystander—it actively promotes MM by blocking cell death and accelerating division, likely via sponging miRNAs that regulate tumor suppressors.
| Research Tool | Function/Application | Example in circ_0001821 Studies |
|---|---|---|
| siRNA / shRNA | Knocks down circRNA to assess function | Validated circ_0001821's role in proliferation & apoptosis 1 |
| qRT-PCR Primers | Backsplice-specific primers quantify circRNA levels | Detected circ_0001821 in patient BM samples & cell lines 1 4 |
| RNase R Treatment | Digests linear RNAs; enriches circRNAs for sequencing | Confirmed circular structure of circ_0001821 2 6 |
| Exosome Isolation Kits | Isolate vesicles from blood/BM to detect circRNA biomarkers | Used in MM studies to find exo-circRNAs (e.g., circMYC) 7 |
| miRNA Mimics/Inhibitors | Tests circRNA's "sponge" effect on miRNAs | Identified miRNA targets of other MM circRNAs (e.g., miR-338-3p) 3 6 |
| (-)-Carveol | 308363-12-4 | C10H16O |
| lipid X(2-) | C34H64NO12P-2 | |
| CS5 Peptide | 107978-81-4 | C107H158N28O34 |
| Phospholine | C4H7P | |
| Diaminozinc | H4N2Zn |
circ_0001821 levels in bone marrow or blood could stratify patients at diagnosis. Combined with tools like ISS staging, it enhances risk prediction—high levels signal 3.71x higher mortality risk 1 4 . Meta-analyses confirm circRNAs collectively offer 82% sensitivity and 76% specificity for MM detection 4 .
Silencing circ_0001821 (e.g., siRNA) reduced MM growth experimentally. Similar approaches are being tested for other circRNAs using antisense oligonucleotides (ASOs) or CRISPR-based tools 6 . Its role in suppressing Caspase-3 also suggests synergy with pro-apoptotic drugs.
circRNAs like circ_0007841 (structurally similar to circ_0001821) confer resistance to bortezomib and doxorubicin by upregulating drug-efflux pumps (e.g., ABCG2) 3 . Targeting circ_0001821 could re-sensitize relapsed tumors.
Circ_0001821 exemplifies how once-overlooked RNA circles are rewriting myeloma biology. As a stable biomarker, it offers a liquid biopsy option to track disease. As a therapeutic target, its suppression could stall progression. Future work will focus on:
"In the loops of RNA, we find both the drivers of malignancy and the keys to locking it down." – Adapted from Dr. Alessandro Allegra, University of Messina 6