Therapeutic Potential of microRNA Against Th2-associated Immune Disorders

Kumar, Sunil; Ashraf, Muhammad; Kumar, Anil; Bae, Yong-Soo

doi:10.2174/1568026621666210303150235

Cited by 8 publications

(5 citation statements)

References 148 publications

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“…The study of underlying mechanism revealed that miR-150 targeted genes are mainly associated with RNA metabolism (synthesis, export, splicing and stability), transcriptional regulation, Wnt-signalling and mammalian target of rapamycin (mTOR)signalling pathways. Interestingly, knockdown of any of these miR-150 downregulated targets (TET3, EIF4B, FOXO4B and PRKCA) showed anti-leukaemia activity similar to miR-150 restoration therapy [ 102 ]. Conclusively, these results authenticate the druggable value of miR-150 in treating AML and as a novel candidate for therapeutic drug development [ 101 ].…”

Section: Microrna In Amlmentioning

confidence: 99%

Immunotherapeutic Potential of m6A-Modifiers and MicroRNAs in Controlling Acute Myeloid Leukaemia

Kumar

Nagpal

Kumar³

et al. 2021

Biomedicines

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Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have been predominantly focused on DNA methylation, histone modifications, and chromatin remodelling. Epitranscriptomics is an emerging field that encompasses the study of RNA modifications that do not affect the RNA sequence but affect functionality via a series of RNA binding proteins called writer, reader and eraser. Several kinds of epi-RNA modifications are known, such as 6-methyladenosine (m6A), 5-methylcytidine (m5C), and 1-methyladenosine. M6A modification is the most studied and has large therapeutic implications. In this review, we have summarised the therapeutic potential of m6A-modifiers in controlling haematological disorders, especially acute myeloid leukaemia (AML). AML is a type of blood cancer affecting specific subsets of blood-forming hematopoietic stem/progenitor cells (HSPCs), which proliferate rapidly and acquire self-renewal capacities with impaired terminal cell-differentiation and apoptosis leading to abnormal accumulation of white blood cells, and thus, an alternative therapeutic approach is required urgently. Here, we have described how RNA m6A-modification machineries EEE (Editor/writer: Mettl3, Mettl14; Eraser/remover: FTO, ALKBH5, and Effector/reader: YTHDF-1/2) could be reformed into potential druggable candidates or as RNA-modifying drugs (RMD) to treat leukaemia. Moreover, we have shed light on the role of microRNAs and suppressors of cytokine signalling (SOCS/CISH) in increasing anti-tumour immunity towards leukaemia. We anticipate, our investigation will provide fundamental knowledge in nurturing the potential of RNA modifiers in discovering novel therapeutics or immunotherapeutic procedures.

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Section: Microrna In Amlmentioning

confidence: 99%

Immunotherapeutic Potential of m6A-Modifiers and MicroRNAs in Controlling Acute Myeloid Leukaemia

Kumar

Nagpal

Kumar³

et al. 2021

Biomedicines

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“…ICB therapy combined miRNA [40][41][42][43][44] Before coming to the main stream of this review, a very logical question arises: (i) why even after so strong therapeutic approaches still some cancer cells escape these immune surveillance mechanisms? (ii) What could be the best possible combinations to overcome the issues associated with drug-resistance and high-dose antibody toxicities [72][73][74][75] and (iii) what would be the best diagnostic biomarkers or alternative strategies to completely eliminate these cancerous cells?…”

Section: Hypo-methylation Increases Pd-l1 and Pd-l2 Expressionmentioning

confidence: 99%

“…(iv) Precision medicines/personalized therapy: combining immunotherapy targeting intracellular immune checkpoints (CISH/SOCS-1) in specific immune cells [ 130 , 131 ]. (v) Molecular medicine: epigenetic modifiers targeting DNA, histone proteins and chromatin remodelers [ 22 , 132 ] and (vi) microRNAs [ 41 , 133 , 134 ] ( Table 1 and Table 3 , Figure 1 ). The detail of ICB-therapy and strategies to overcome ICB-drug resistance is well described in this review [ 75 ], however covering all is out of scope of this review.…”

Section: Milestones In Icb Therapeuticsmentioning

confidence: 99%

“…The significance of ‘microRNAs’ also cannot be ignored because of their versatile roles in regulating numerous genes associated with immune checkpoint inhibitors. Kumar and colleagues have extensively described the therapeutic potential of microRNAs in treating DC-mediated Th1/Th2-associated immune disorders [ 41 , 192 ]. However, this section highlights some of the recent advancements in the utilization of ‘microRNAs’ in improving the efficacy of ICB-therapeutics.…”

Section: Micrornas and Epigenetic Modifiers (Dna And Histone Proteins) In Icb-therapymentioning

confidence: 99%

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Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH

Kumar

Sarthi

Mani

et al. 2021

Cells

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Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, some cancer patients escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required urgently. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidence, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N6A-modification machineries which can be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover, and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signaling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine.

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“…The significance of 'microRNAs' also cannot be ignored because of their versatile roles in regulating numerous genes associated with immune checkpoint inhibitors. Kumar and colleagues have extensively described the therapeutic potential of microRNAs in treating DC-mediated Th1/Th2-associated immune disorders [48,104]. However, this section highlights some of the recent advancements in the utilization of 'microRNAs' in improving the efficacy of ICB-therapeutics.…”

Section: Micrornas In Icb-therapeuticsmentioning

confidence: 99%

Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-targeting Intracellular Checkpoint CISH

Kumar¹,

Sarthi²,

Mani³

et al. 2021

Preprint

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Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, still some cancer patient escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required instantly. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidences, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N6A-modification machineries which could be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signalling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine.

show abstract

Therapeutic Potential of microRNA Against Th2-associated Immune Disorders

Cited by 8 publications

References 148 publications

Immunotherapeutic Potential of m6A-Modifiers and MicroRNAs in Controlling Acute Myeloid Leukaemia

Immunotherapeutic Potential of m6A-Modifiers and MicroRNAs in Controlling Acute Myeloid Leukaemia

Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH

Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-targeting Intracellular Checkpoint CISH

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