The Tumor Suppressor Roles and Mechanisms of MiR-491 in Human Cancers

Sadri, Farzad; Hosseini, Seyede Fatemeh; Aghayei, Atena; Fereidouni, Mohammad; Rezaei, Zohreh

doi:10.1089/dna.2022.0274

Cited by 5 publications

(2 citation statements)

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“…miRNAs can be secreted into circulation in extracellular fluids and shuttled to target cells via extracellular vesicles, including exosomes, microvesicles, and apoptotic bodies under various physiologic and pathologic conditions, enabling them to function as For example, as illustrated in Figure 4, in recent years, many circulating miRNAs identified as potential diagnostic and prognostic biomarkers in pancreatic cancer have been reported in the literature [66,[185][186][187][188][189].…”

Section: Mirnas As Potential Biomarkersmentioning

confidence: 99%

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Circulating microRNAs as Potential Biomarkers in Pancreatic Cancer—Advances and Challenges

Seyhan

2023

IJMS

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There is an urgent unmet need for robust and reliable biomarkers for early diagnosis, prognosis, and prediction of response to specific treatments of many aggressive and deadly cancers, such as pancreatic cancer, and liquid biopsy-based miRNA profiling has the potential for this. MiRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many cancers, functioning as either oncomes or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling of dysregulated miRNAs in pancreatic cancer has been shown to correlate with disease diagnosis, indicate optimal treatment options and predict response to a specific therapy. Specific miRNA signatures can track the stages of pancreatic cancer and hold potential as diagnostic, prognostic, and predictive markers, as well as therapeutics such as miRNA mimics and miRNA inhibitors (antagomirs). Furthermore, identified specific miRNAs and genes they regulate in pancreatic cancer along with downstream pathways can be used as potential therapeutic targets. However, a limited understanding and validation of the specific roles of miRNAs, lack of tissue specificity, methodological, technical, or analytical reproducibility, harmonization of miRNA isolation and quantification methods, the use of standard operating procedures, and the availability of automated and standardized assays to improve reproducibility between independent studies limit bench-to-bedside translation of the miRNA biomarkers for clinical applications. Here I review recent findings on miRNAs in pancreatic cancer pathogenesis and their potential as diagnostic, prognostic, and predictive markers.

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Section: Mirnas As Potential Biomarkersmentioning

confidence: 99%

“…Concerning their utility as potential biomarkers in pancreatic cancer, several studies have reported that the expression of several circulating miRNAs is altered in pancreatic cancer [14,62,66,67,129,130,[185][186][187][188][189][220][221][222][223][224].…”

Section: Circulating Mirnas As Potential Biomarkers In Pancreatic Cancermentioning

confidence: 99%

Circulating microRNAs as Potential Biomarkers in Pancreatic Cancer—Advances and Challenges

Seyhan

2023

IJMS

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The suppression of OTUD7B by miR‐491‐5p enhances the ubiquitination of VEGFA to suppress vascular mimicry in non‐small cell lung cancer

Chen,

He,

Zhong

et al. 2024

The Journal of Gene Medicine

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BackgroundNon‐small cell lung cancer (NSCLC) is the main type of lung cancer with high morbidity and mortality. Vascular mimicry (VM), a distinct microcirculation model in tumors that differs from classical angiogenesis, is strongly associated with poor clinical outcomes in cancer patients. miR‐491‐5p has been reported to prevent NSCLC progression, including proliferation, metastasis, and angiogenesis. However, the effect and mechanism of miR‐491‐5p on VM have not been studied in NSCLC.MethodsThe expression of miR‐491‐5p was detected by quantitative reverse transcription PCR (qPCR) and fluorescence in situ hybridization (FISH). Cell counting kit‐8 (CCK‐8) and 5‐ethynyl‐2′‐deoxyuridine (EdU) staining assays were used to examine cell growth. Tube formation assay was used to assess VM in NSCLC cells. Immunohistochemistry (IHC) and western blot were performed to detect protein expression. Immunoprecipitation was used to confirm the interaction between OTU deubiquitinase 7B (OTUD7B) and vascular endothelial growth factor A (VEGFA), and the level of ubiquitinated VEGFA. A nude mouse tumorigenesis model was used to evaluate the carcinogenic capacity of NSCLC cells in vivo. Luciferase reporter assay was used to identify the potential target of miR‐491‐5p.ResultsMiR‐491‐5p was found downregulated in NSCLC tissues, and miR‐491‐5p deficiency was strongly associated with angiogenesis. miR‐491‐5p mimics suppressed cell viability, migration, and VM. Conversely, an inhibitor of miR‐491‐5p had the opposite effect. OTUD7B, a deubiquitinase, was identified as a downstream target of miR‐491‐5p. A luciferase reporter assay indicated that miR‐491‐5p directly binds to the 3′UTR of OTUD7B. Moreover, mimics of miR‐491‐5p caused a significant reduction in the OTUD7B protein in NSCLC cells, and an inhibitor of miR‐491‐5p stabilized the OTUD7B protein. In addition, overexpression of OTUD7B promoted cell proliferation, migration, and VM, similar to the effects of an inhibitor of miR‐491‐5p. Further exploration revealed that OTUD7B interacts with VEGFA and that the miR‐491‐5p‐OTUD7B axis modulates the ubiquitination of VEGFA. The rescue experiment indicated that OTUD7B compromised the inhibitory effects of miR‐491‐5p on the cellular function of NSCLC cells.ConclusionsOverall, our study first proved that miR‐491‐5p impedes VM by suppressing OUTD7B and promoting the ubiquitination of VEGFA. The miR‐491‐5p/OTUD7B axis may be a novel target for antiangiogenic therapy in NSCLC.

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