MicroRNA-34a: A Versatile Regulator of Myriads of Targets in Different Cancers

Farooqı, Ammad Ahmad; Tabassum, Sobia; Ahmad, Aamir

doi:10.3390/ijms18102089

Cited by 49 publications

(39 citation statements)

References 69 publications

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“…miR-34a expression is lost or downregulated in a wide variety of cancers, and is generally considered to act as a tumor suppressor miRNA by influencing the expression of a plethora of genes involved in cell proliferation, autophagy, metabolism, apoptosis, senescence, stemness, epithelial-to-mesenchymal transition (EMT) and motility [29,30]. miR-34a targets identified in the context of bladder cancer cells include CD44 [27] and TCF1 and LEF1 [31].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-Based Approach

Cavallari

Grassi

Bianco

et al. 2020

Cancers

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Robust non-invasive tests for prognostic stratification of bladder cancer (BCa) patients are in high demand. Following a comprehensive analysis of studies on BCa, we selected a panel of 29 microRNAs (miRNAs) and analyzed their levels in urine and plasma samples in a prospective cohort of 63 BCa patients (32 at high risk of recurrence and 31 low-risk cases) and 37 healthy controls using RT-qPCR. To design an assay suitable for large-scale testing, we applied a hierarchical pipeline to select the miRNAs that were not affected by confounding factors such as haematuria and urine specific gravity, and exceeded stringent cut-off criteria (fold change > 2.5 and p-value < 0.005). Using a two-step decision tree based on the urine levels of miR-34a-5p, miR-200a-3p and miR-193a-5p, normalized against miR-125b-5p, patients could be classified as high- or low-risk with a sensitivity of 0.844, specificity of 0.806 and accuracy of 0.825. Furthermore, univariate Cox proportional hazards regression analyses indicated that increased urine levels of miR-29a-3p, miR-34a-5p, miR-193a-5p, miR-200c-3p, miR-205-5p and miR-532-5p were associated with a shorter event-free survival (hazard ratios > 3.1, p-value < 0.05). Taken together, our findings suggest that measuring the urine levels of these miRNAs could provide a novel cost-effective, noninvasive test for risk assessment of BCa patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-Based Approach

Cavallari

Grassi

Bianco

et al. 2020

Cancers

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“…Despite RNA diversity, microRNAs are the main targets for research and clinical applications [87]. As an example, the microRNA family MiR-34 is silenced in a wide variety of cancers and seems to regulate important genes related to cell cycle control and proliferation, such as MYC [88,89]. Synlogic Therapeutics, a biopharmaceutical company, synthesized the first microRNA similar to mir-34, MRX34 [89].…”

Section: Ncrna Targets and Ncrna Based Therapymentioning

confidence: 99%

Epidrugs: targeting epigenetic marks in cancer treatment

et al. 2019

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Growing evidence suggests that aberrant epigenetic regulation of gene function is strongly related to the genesis of cancer. Unlike genetic mutations, the ability to reprogram the epigenetic landscape in the cancer epigenome is one of the most promising target therapies in both treatment and reversibility of drug resistance. Epigenetic alterations in cancer development and progression may be the basis for the individual variation in drug response. Thus, this review focuses on the emerging area of pharmaco(epi)genomics, specifically highlighting epigenetic reprogramming during tumorigenesis and how epigenetic markers are targeted as a therapy (epidrugs) and the clinical implications of this for cancer treatment.

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“…Therefore, the restoration of miRNA-34a physiological levels is now a promising tool to counteract tumor progression (Farooqi et al, 2017).…”

Section: Delivery Of Autophagy-related Mirna-34a With Nanoparticlesmentioning

confidence: 99%

Nanomaterials for Autophagy-Related miRNA-34a Delivery in Cancer Treatment

et al. 2020

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Autophagy is an evolutionary conserved physiological process with a fundamental role during development, differentiation, and survival of eukaryotic cells. On the other hand, autophagy dysregulation is observed in many pathological conditions, including cancer. In particular, tumor growth and progression are accompanied and promoted by increased autophagy that allows cancer cells to escape apoptosis and to proliferate also in harsh microenvironments. It is, therefore, clear that the impairment of the autophagic process may represent a valid strategy to inhibit or reduce cancer growth and progression. Among the plethora of molecular players controlling cancer growth, a group of small endogenous noncoding RNAs called microRNAs (miRNAs) has recently emerged. In fact, miRNAs can act as either oncogenes or oncosuppressors depending on their target genes. Moreover, among miRNAs, miRNA-34a has been connected with both tumor repression and autophagy regulation, and its expression is frequently lost in many cancers. Therefore, enforced expression of miRNA-34a in cancer cells may represent a valid strategy to reduce cancer growth. However, such strategy is limited by the fast biodegradation and short half-life of miRNA-34a and by the lack of an efficient intracellular delivery system. The following review describes the autophagic process and its role in cancer as well as the role of miRNAs in general and miRNA-34a in particular in regulating tumor growth by modulating autophagy. Finally, we describe the use of nanoparticles as a promising strategy to selectively deliver miRNA-34a to tumor cells for therapeutic and diagnostic purposes.

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MicroRNA-34a: A Versatile Regulator of Myriads of Targets in Different Cancers

Cited by 49 publications

References 69 publications

Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-Based Approach

Prognostic Stratification of Bladder Cancer Patients with a MicroRNA-Based Approach

Epidrugs: targeting epigenetic marks in cancer treatment

Nanomaterials for Autophagy-Related miRNA-34a Delivery in Cancer Treatment

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