ABSTRACT
Cancer remains a challenging disease worldwide, necessitating innovative approaches to better comprehend its underlying molecular mechanisms and devise effective therapeutic strategies. Over the past decade, microRNAs (miRNAs) have emerged as crucial players in cancer progression due to their regulatory roles in various cellular processes. Moreover, the involvement of unwanted soluble receptors has gained increasing attention because they contribute to tumorigenesis or drug resistance by disrupting normal signaling pathways and neutralizing ligands. This comprehensive review explores the intricate interplay between miRNAs and unwanted-soluble receptors in the context of cancer biology. This study provides an analysis of the regulatory interactions between miRNAs and these receptors, elucidating how miRNAs can either suppress or enhance their expression. MiRNAs can directly target receptor transcripts, thereby regulating soluble receptor levels. They also modulate the proteolytic cleavage of membrane-bound receptors into soluble forms by targeting sheddases, such as ADAMs and MMPs. Furthermore, the review delves into the therapeutic potential of manipulating miRNAs to modulate unwanted soluble receptors. Various strategies, including synthetic miRNA mimics or anti-miRNAs, hold promise for restoring or inhibiting miRNA function to counteract aberrant receptor activity. Moreover, exploring miRNA-based delivery systems may provide targeted and precise therapies that minimizing off-target effects. In conclusion, this review sheds light on the intricate regulatory networks involving miRNAs and unwanted soluble receptors in cancer biology thereby uncovering novel therapeutic targets, and paving the way for developing innovative anti-cancer therapies.
ABSTRACT
Background: One of the acute hematologic malignancies is acute lymphoblastic leukemia (ALL), which is formed in B or T lymphocyte stem cells. Regarding the increasing tendency to herbal and marine studies and unclear characteristics of Cassiopea andromeda Venom, this study was performed to determine its effects on Jurkat cells as a model for T-ALL. Materials and Methods: In this experimental study, the cells were treated with a variety of concentrations of Cassiopea andromeda venom at different periods and times. Growth inhibition and toxic effects of Cassiopea andromeda Venom were evaluated by methyl thiazole tetrazolium salt reduction (MTT test). The flow cytometry analysis was carried out using 7-aminoactinomycin D (7AAD) and Annexin V stains to evaluate the venom's effect on apoptotic pathways. Besides, Real-Time PCR was performed to evaluate the relative gene expression. Results: Cassiopea andromeda venom inhibited the growth of Jurkat cells in a concentration and time manner. Jurkat cell growth was inhibited by 48.9% after 72 hours of treatment with 250µg/mL Cassiopea andromeda venom. The venom increased the apoptotic process through the upregulation of p15INK4b and P53 proteins and downregulation of Bcl-2, p21 WAF1/CIP1, and DNMT1 in the Jurkat cell line. Conclusion: Considering the growth inhibitory property of Cassiopea andromeda Venom, we recommend it as a part of combinational medication for treating ALL in animal trials and for other leukemias in vitro studies.
ABSTRACT
BACKGROUND: The role of serum-based biomarkers such as microRNAs in cancer diagnosis has been extensively established. This study aimed to determine the expression levels of bioinformatically selected miRNAs and whether they can be used as biomarkers or a new therapeutic target in patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: The expression levels of serum miR-22, miR-122, miR-217, and miR-367 in 21 ALL patients and 21 healthy controls were measured using quantitative real-time PCR. The receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) was used to assess candidate miRNAs' diagnostic value as a biomarker. RESULTS: The results showed that miR-217 was markedly decreased in patients with ALL compared to controls. Moreover, miR-22, miR-122, and miR-367 were found to be upregulated. Furthermore, ROC analysis showed that serum miR-217 and miR-367 could differentiate ALL patients from healthy individuals, while miR-22 has approximate discriminatory power that requires further investigation. CONCLUSION: These results provide promising preliminary evidence that circulating miR-217 and miR-367 could be considered potent diagnostic biomarkers and therapeutic goals in this disease.
