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MiR-223-3p in Cancer Development and Cancer Drug Resistance: Same Coin, Different Faces
Davide Barbagallo1,2, Donatella Ponti3, Barbara Bassani4
1Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "Giovanni Sichel", University of Catania, Via Santa Sofia 89, 95123 Catania, Italy.
Abstract:
MicroRNAs (miRNAs) are mighty post-transcriptional regulators in cell physiology and pathophysiology. In this review, we focus on the role of miR-223-3p (henceforth miR-223) in various cancer types. MiR-223 has established roles in hematopoiesis, inflammation, and most cancers, where it can act as either an oncogenic or oncosuppressive miRNA, depending on specific molecular landscapes. MiR-223 has also been linked to either the sensitivity or resistance of cancer cells to treatments in a context-dependent way. Through this detailed review, we highlight that for some cancers (i.e., breast, non-small cell lung carcinoma, and glioblastoma), the oncosuppressive role of miR-223 is consistently reported in the literature, while for others (i.e., colorectal, ovarian, and pancreatic cancers, and acute lymphocytic leukemia), an oncogenic role prevails. In prostate cancer and other hematological malignancies, although an oncosuppressive role is frequently described, there is less of a consensus. Intriguingly, NLRP3 and FBXW7 are consistently identified as miR-223 targets when the miRNA acts as an oncosuppressor or an oncogene, respectively, in different cancers. Our review also describes that miR-223 was increased in biological fluids or their extracellular vesicles in most of the cancers analyzed, as compared to healthy or lower-risk conditions, confirming the potential application of this miRNA as a diagnostic and prognostic biomarker in the clinic.
Insights
MicroRNA-223 (miR-223) plays a dual role in cancer, acting as either an oncogene or tumor suppressor depending on the cancer type. Elevated miR-223 in bodily fluids suggests its potential as a cancer biomarker.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are key post-transcriptional regulators influencing cell functions and diseases.
- miR-223-3p (miR-223) is implicated in hematopoiesis, inflammation, and diverse cancer types, exhibiting context-dependent oncogenic or oncosuppressive activities.
- miR-223's role in cancer treatment sensitivity or resistance is also context-dependent.
Purpose of the Study:
- To review the multifaceted roles of miR-223 in various human cancers.
- To elucidate the dual oncogenic and oncosuppressive functions of miR-223 across different cancer types.
- To explore the potential of miR-223 as a diagnostic and prognostic biomarker in oncology.
Main Methods:
- Comprehensive literature review of studies investigating miR-223 in cancer.
- Analysis of miR-223's expression patterns and functional roles in different malignancies.
- Identification of key miR-223 targets, such as NLRP3 and FBXW7, in oncogenic and oncosuppressive contexts.
Main Results:
- miR-223 exhibits an oncosuppressive role in breast cancer, non-small cell lung carcinoma, and glioblastoma.
- An oncogenic role for miR-223 prevails in colorectal, ovarian, pancreatic cancers, and acute lymphocytic leukemia.
- miR-223 shows variable roles in prostate cancer and hematological malignancies, with NLRP3 and FBXW7 identified as key targets.
- Increased miR-223 levels were observed in biological fluids and extracellular vesicles across many analyzed cancers.
Conclusions:
- miR-223 demonstrates a context-specific dual role in cancer progression and suppression.
- The expression levels of miR-223 in biofluids indicate its potential as a valuable biomarker for cancer diagnosis and prognosis.
- Understanding miR-223's intricate roles is crucial for developing targeted cancer therapies.
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