MicroRNA-122 mimic/microRNA-221 inhibitor combination as a novel therapeutic tool against hepatocellular carcinoma

Hassan, Marwa; Elzallat, Mohamed; Aboushousha, Tarek; Elhusseny, Yasmine; El‐Ahwany, Eman

doi:10.1016/j.ncrna.2022.11.005

Cited by 14 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It makes up about 70% of the miRNA population in the adult liver. 44 A small amount of ADAR1 has limited editing effects on a very large number of miR-122 molecules. In this case, ADAR1 collaborating with Dicer may have a dominant role in promoting the generation of mature miR-122, resulting in a positive correlation between ADAR1 and miR-122.…”

Section: Discussionmentioning

confidence: 99%

ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling

Liu,

Xie,

Duan

et al. 2023

J Clin Transl Hepatol

View full text Add to dashboard Cite

Background and Aims As sepsis progresses, immune cell apoptosis plays regulatory roles in the pathogenesis of immunosuppression and organ failure. We previously reported that adenosine deaminases acting on RNA-1 (ADAR1) reduced intestinal and splenic inflammatory damage during sepsis. However, the roles and mechanism of ADAR1 in sepsis-induced liver injury remain unclear. Methods We performed transcriptome and single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with sepsis to investigate the effects of ADAR1 on immune cell activities. We also employed a cecal ligation and puncture (CLP) sepsis mouse model to evaluate the roles of ADAR1 in sepsis-induced liver injury. Finally, we treated murine RAW 264.7 macrophages with lipopolysaccharide to explore the underlying ADAR1-mediated mechanisms in sepsis. Results PBMCs from patients with sepsis had obvious apoptotic morphological features. Single-cell RNA sequencing indicated that apoptosis-related pathways were enriched in monocytes, with significantly elevated ADAR1 and BCL2A1 expression in severe sepsis. CLP-induced septic mice had aggravated liver injury and Kupffer cell apoptosis that were largely alleviated by ADAR1 overexpression. ADAR1 directly bound to pre-miR-122 to modulate miR-122 biosynthesis. miR-122 was an upstream regulator of BCL2A1. Furthermore, ADAR1 also reduced macrophage apoptosis in mice with CLP-induced sepsis through the miR-122/BCL2A1 signaling pathway and protected against sepsis-induced liver injury. Conclusions The findings show that ADAR1 alleviates macrophage apoptosis and sepsis-induced liver damage through the miR-122/BCL2A1 signaling pathway. The study provides novel insights into the development of therapeutic interventions in sepsis.

show abstract

Section: Discussionmentioning

confidence: 99%

ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling

Liu,

Xie,

Duan

et al. 2023

J Clin Transl Hepatol

View full text Add to dashboard Cite

show abstract

“…miR-221 and miR-122 mimics, which are examples of miRNA mimics and inhibitors, have been found to have beneficial effects by effectively decreasing cell growth, signs of inflammation, and the formation of new blood vessels [189]. The efficacy of MRX34, an miR-34a mimic, was evaluated in a phase I clinical trial (NCT01829971) involving advanced solid tumours, including HCC ( Hassan et al, 2023 ). However, the end of the study period was driven by significant adverse effects.…”

Section: Advancements In Future Therapeutic Strategiesmentioning

confidence: 99%

Genetic Alchemy unveiled: MicroRNA-mediated gene therapy as the Artisan craft in the battlefront against hepatocellular carcinoma—a comprehensive chronicle of strategies and innovations

Murshed,

Alnoud,

Ahmad

et al. 2024

Front. Genet.

View full text Add to dashboard Cite

Investigating therapeutic miRNAs is a rewarding endeavour for pharmaceutical companies. Since its discovery in 1993, our understanding of miRNA biology has advanced significantly. Numerous studies have emphasised the disruption of miRNA expression in various diseases, making them appealing candidates for innovative therapeutic approaches. Hepatocellular carcinoma (HCC) is a significant malignancy that poses a severe threat to human health, accounting for approximately 70%–85% of all malignant tumours. Currently, the efficacy of several HCC therapies is limited. Alterations in various biomacromolecules during HCC progression and their underlying mechanisms provide a basis for the investigation of novel and effective therapeutic approaches. MicroRNAs, also known as miRNAs, have been identified in the last 20 years and significantly impact gene expression and protein translation. This atypical expression pattern is strongly associated with the onset and progression of various malignancies. Gene therapy, a novel form of biological therapy, is a prominent research area. Therefore, miRNAs have been used in the investigation of tumour gene therapy. This review examines the mechanisms of action of miRNAs, explores the correlation between miRNAs and HCC, and investigates the use of miRNAs in HCC gene therapy.

show abstract

“…In addition, there are miRNAs mimics and inhibitors, such as the miR-221 inhibitor and miR-122 mimic, that demonstrated favorable effects as they significantly reduce proliferation and pro-inflammatory markers, as well as neoangiogenesis [ 189 ]. Meanwhile, there is a phase I clinical trial (NCT01829971) for MRX34 which constitutes an miR-34a mimic that is evaluated in advanced solid tumors, including HCC [ 190 ].…”

Section: Future Therapeutic Opportunitiesmentioning

confidence: 99%

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

Koustas

Trifylli²,

Sarantis

et al. 2023

IJMS

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is still low. Shedding light on the multiplex genetic and epigenetic background of HCC, such as on the emerging role of microRNAs, is considered quite promising for the diagnosis and the prediction of this malignancy, as well as for combatting drug resistance. MicroRNAs (miRNAs) constitute small noncoding RNA sequences, which play a key role in the regulation of several signaling and metabolic pathways, as well as of pivotal cellular functions such as autophagy, apoptosis, and cell proliferation. It is also demonstrated that miRNAs are significantly implicated in carcinogenesis, either acting as tumor suppressors or oncomiRs, while aberrations in their expression levels are closely associated with tumor growth and progression, as well as with local invasion and metastatic dissemination. The arising role of miRNAs in HCC is in the spotlight of the current scientific research, aiming at the development of novel therapeutic perspectives. In this review, we will shed light on the emerging role of miRNAs in HCC.

show abstract

MicroRNA-122 mimic/microRNA-221 inhibitor combination as a novel therapeutic tool against hepatocellular carcinoma

Cited by 14 publications

References 44 publications

ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling

ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling

Genetic Alchemy unveiled: MicroRNA-mediated gene therapy as the Artisan craft in the battlefront against hepatocellular carcinoma—a comprehensive chronicle of strategies and innovations

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

Contact Info

Product

Resources

About