Flavonoid display ability to target microRNAs in cancer pathogenesis

Singh, Shilpi; Raza, Waseem; Parveen, Shabana; Meena, Abha; Luqman, Suaib

doi:10.1016/j.bcp.2021.114409

Cited by 16 publications

(12 citation statements)

References 366 publications

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“…Furthermore, a clinical study on patients undergoing prostatectomy consuming EGCG showed an increase in plasma TIMP3 levels (Deb et al, 2019). Dietary flavonoids have potential to modulate non-coding RNAs, including miRNAs in cancer (Ahmed et al, 2020;Yang et al, 2020;Singh et al, 2021). In a recent in vivo study by Kang et al, revealed that oral administration of EGCG suppresses miR483-3p induced metastasis of hepatocellular carcinoma (Kang et al, 2021).…”

Section: Cancer Prevention and Therapy By Epigenetically Active Flavonoidsmentioning

confidence: 99%

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Role of Flavonoids as Epigenetic Modulators in Cancer Prevention and Therapy

Fatima¹,

Baqri²,

Bhattacharya

et al. 2021

Front. Genet.

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Epigenetic regulation involves reversible changes in histones and DNA modifications that can be inherited without any changes in the DNA sequence. Dysregulation of normal epigenetic processes can lead to aberrant gene expression as observed in many diseases, notably cancer. Recent insights into the mechanisms of DNA methylation, histone modifications, and non-coding RNAs involved in altered gene expression profiles of tumor cells have caused a paradigm shift in the diagnostic and therapeutic approaches towards cancer. There has been a surge in search for compounds that could modulate the altered epigenetic landscape of tumor cells, and to exploit their therapeutic potential against cancers. Flavonoids are naturally occurring phenol compounds which are abundantly found among phytochemicals and have potentials to modulate epigenetic processes. Knowledge of the precise flavonoid-mediated epigenetic alterations is needed for the development of epigenetics drugs and combinatorial therapeutic approaches against cancers. This review is aimed to comprehensively explore the epigenetic modulations of flavonoids and their anti-tumor activities.

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Section: Cancer Prevention and Therapy By Epigenetically Active Flavonoidsmentioning

confidence: 99%

“…Dietary flavonoids have potential to modulate non-coding RNAs, including miRNAs in cancer ( Ahmed et al, 2020 ; Yang et al, 2020 ; Singh et al, 2021 ). In a recent in vivo study by Kang et al, revealed that oral administration of EGCG suppresses miR483–3p induced metastasis of hepatocellular carcinoma ( Kang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Role of Flavonoids as Epigenetic Modulators in Cancer Prevention and Therapy

Fatima¹,

Baqri²,

Bhattacharya

et al. 2021

Front. Genet.

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“…The ability of flavonoids to affect miRNAs involved in carcinogenesis (review, [ 135 , 136 ]) is particularly relevant in CSCs. Thus, in breast cancer cells, exposure to Glabridin, a phytochemical from the root of Glycyrrhiza glabra, upregulated miR-148a via promoter de-methylation, leading to the suppression of SMAD2 and decrease in CSC-like properties [ 137 ].…”

Section: Anti-csc Activity Of Flavonoids Mediated By Modulation Of Micrornasmentioning

confidence: 99%

Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

Meerson

Khatib

Mahajna

2021

IJMS

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Cancer stem cells (CSC) have been identified in several types of solid tumors. In some cases, CSC may be the source of all the tumor cells, the cause of the tumor’s resistance to chemotherapeutic agents, and the source of metastatic cells. Thus, a combination therapy targeting non-CSC tumor cells as well as specifically targeting CSCs holds the potential to be highly effective. Natural products (NPs) have been a historically rich source of biologically active compounds and are known for their ability to influence multiple signaling pathways simultaneously with negligible side effects. In this review, we discuss the potential of NPs in targeting multiple signaling pathways in CSC and their potential to augment the efficacy of standard cancer therapy. Specifically, we focus on the anti-CSC activities of flavonoids, FDA-approved drugs originating from natural sources. Additionally, we emphasize the potential of NPs in targeting microRNA-mediated signaling, given the roles of microRNA in the maintenance of the CSC phenotype.

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“…The characteristic patterns of miRNA in various cancer tissues are helpful in the prognosis, diagnosis, and treatment of cancer (Condrat et al, 2020;Peng & Croce, 2016;Wang, Peng, Wang, Qin, & Xue, 2018). Besides, these are involved in the survival of cancer stem-like cells and epithelial-mesenchymal transition (Singh, Raza, et al, 2021). Since the deregulation of oncogenic miRNAs has been established and oligonucleotide-based gene therapy intervention approaches are used; however, their application is limited due to chemical instability, fast degradation, inappropriate biodistribution, and low cell permeability (Gagliardi & Ashizawa, 2021;Lundin, Gissberg, & Smith, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…They exert various healthpromoting effects against various diseases, including cancer, and also provide a template for novel designing of unique molecules to regulate altered signaling pathways and gene expression in cancer cells . Various flavonoids including EGCG, morin, apigenin, quercetin, formononetin, kaempferol, rhammetin, genistein, baicalein, luteolin, emodin, silymarin, and so on also modulate the expression of various miRNAs in cancer cells thereby suppressing the proliferation, angiogenesis, and migration of cancer cells (Singh, Raza, Parveen, Meena, & Luqman, 2021). Micro-RNAs (miRNAs) are endogenous and non-protein-coding nucleotides involved in regulating post-transcriptional gene expression.…”

Section: Introductionmentioning

confidence: 99%

Dietary flavonoid narirutin as a prospective antagonist of oncogenic pri/pre‐microRNAs

Singh

Srivastava

Meena

et al. 2022

Phytotherapy Research

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MicroRNAs (miRNAs) are involved in cancer progression via translational degradation in a sequence-specific manner of the 3 0 -untranslated region (3 0 UTR) of messenger RNA (mRNA). The involvement of miRNA in the biological progression of various cancer types is considered to be a potential target. Primary miRNA (pri-miRNA) and precursor-miRNA (pre-miRNA) synthesize the miRNA by dicer-catalyzed processes thus targeting pri/pre-miRNA by phytochemicals is amongst the appropriate approaches for anticancer therapies. Flavonoids category of phytochemicals is wellknown for its chemotherapeutic and chemopreventive potential against multiple cancer types. However, the molecular interactions of flavonoids with miRNAs are not reported so far. Thus, this study aims to identify the promising flavonoids as the antagonist of miRNAs (pre-miR21, pri-miR-208a, pri-miR-378a, pri-miR320b, pri-miR-300, pri-miR-19b, and pre-miR-20b) using molecular docking simulations studies.Among the tested flavonoids, narirutin showed highest binding energy (À11.7 kcal/ mol) against pri-miR19b followed by pri-miR-378a (À11.4 kcal/mol) > pri-miR320b (À11.2 kcal/mol) = pri-miR-300 (À11.2 kcal/mol) > pri-miR-208a (À9.0 kcal/mol) > pre-miR-20b (À 8.3 kcal/mol). The molecular dynamic simulation experiment confirmed that narirutin destabilizes the tertiary structure of pri-miRNA in comparison to apo-RNA. The finding indicates that narirutin binding with pre-miRNA causes disruption of pri-RNA structure that creates a loss of DICER-pre-miRNA interactions by hindering the pre-miRNA synthesis, thereby affecting miRNA processing. Further pharmacokinetics and toxicity prediction revealed that it is non-carcinogenic, nonmutagenic, and does not inhibit the CYPs activity. Thus, narirutin could be a possible antagonist of oncogenic miRNAs, therefore could be useful for miRNA-targeted cancer prevention and treatment.

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Flavonoid display ability to target microRNAs in cancer pathogenesis

Cited by 16 publications

References 366 publications

Role of Flavonoids as Epigenetic Modulators in Cancer Prevention and Therapy

Role of Flavonoids as Epigenetic Modulators in Cancer Prevention and Therapy

Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

Dietary flavonoid narirutin as a prospective antagonist of oncogenic pri/pre‐microRNAs

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