Rebound increase in microRNA levels at the end of 5-FU-based therapy in colorectal cancer patients

Badr, Doaa; Fouad, Mariam A.; Hussein, Marwa; Salem, Salem; Zekri, Abdelrahman; Shouman, Samia

doi:10.1038/s41598-023-41030-7

Cited by 4 publications

(2 citation statements)

References 64 publications

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“…These levels had been reduced after 3 months of 5-FU-based therapy and then significantly increased after 6 months in responder patients compared to non-responders. miRNA19a-3p exhibited a noteworthy pattern of change in subgroups of patients with high ERK, EGFR, and PTEN protein levels, and its level after 6 months of 5-FU-based therapy had significant implications for the hazard of increased risk of disease recurrence and progression [71]. The potential of circulating miRNAs as diagnostic biomarkers is highly promising.…”

Section: Role Of Mir-17-92 In Responsiveness and Resistance To Therapymentioning

confidence: 99%

Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential

Al-nakhle

2024

CIMB

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Colorectal cancer (CRC) is a complex disease driven by intricate mechanisms, making it challenging to understand and manage. The miR-17-92 cluster has gained significant attention in CRC research due to its diverse functions and crucial role in various aspects of the disease. This cluster, consisting of multiple individual miRNAs, influences critical processes like tumor initiation, angiogenesis, metastasis, and the epithelial–mesenchymal transition (EMT). Beyond its roles in tumorigenesis and progression, miR-17-92′s dysregulation in CRC has substantial implications for diagnosis, prognosis, and treatment, including chemotherapy responsiveness. It also shows promise as a diagnostic and prognostic biomarker, offering insights into treatment responses and disease progression. This review provides a comprehensive overview of recent advancements and the context-dependent role of the miR-17-92 cluster in colorectal cancer, drawing from the latest high-quality published data. It summarizes the established mechanisms governing miR-17-92 expression and the molecular pathways under its influence. Furthermore, it examines instances where it functions as an oncogene or a tumor suppressor, elucidating how cellular contexts dictate its biological effects. Ultimately, miR-17-92 holds promise as a biomarker for prognosis and therapy response, as well as a potential target for cancer prevention and therapeutic interventions. In essence, this review underscores the multifaceted nature of miR-17-92 in CRC research, offering promising avenues for enhancing the management of CRC patients.

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Section: Role Of Mir-17-92 In Responsiveness and Resistance To Therapymentioning

confidence: 99%

Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential

Al-nakhle

2024

CIMB

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“…miRNAs hold great promise as therapeutic agents because they regulate gene expression and influence cellular pathways involved in various diseases, including cancer, cardiovascular disorders, and neurological conditions [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. The therapeutic potential of miRNAs stems from their ability to target multiple genes simultaneously, allowing for the modulation of complex biological processes.…”

Section: Mirnas and Cancer Therapymentioning

confidence: 99%

How MicroRNAs Command the Battle against Cancer

Wu,

Leng,

Sergi

et al. 2024

IJMS

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MicroRNAs (miRNAs) are small RNA molecules that regulate more than 30% of genes in humans. Recent studies have revealed that miRNAs play a crucial role in tumorigenesis. Large sets of miRNAs in human tumors are under-expressed compared to normal tissues. Furthermore, experiments have shown that interference with miRNA processing enhances tumorigenesis. Multiple studies have documented the causal role of miRNAs in cancer, and miRNA-based anticancer therapies are currently being developed. This review primarily focuses on two key points: (1) miRNAs and their role in human cancer and (2) the regulation of tumor suppressors by miRNAs. The review discusses (a) the regulation of the tumor suppressor p53 by miRNA, (b) the critical role of the miR-144/451 cluster in regulating the Itch-p63-Ago2 pathway, and (c) the regulation of PTEN by miRNAs. Future research and the perspectives of miRNA in cancer are also discussed. Understanding these pathways will open avenues for therapeutic interventions targeting miRNA regulation.

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5‐Fluorouracil treatment represses pseudouridine‐containing miRNA export into extracellular vesicles

Qu,

Nelson,

Liu

et al. 2024

J of Extracellular Bio

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Abstract5‐Fluorouracil (5‐FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5‐FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5‐FU on post‐transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell‐cell communication. We found that treatment of colorectal cancer (CRC) cells with 5‐FU represses sEV export of miRNA and snRNA‐derived RNAs, but promotes export of snoRNA‐derived RNAs. Strikingly, 5‐FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5‐FU exposure led to increased levels of cellular small RNAs containing a variety of methyl‐modified bases. These unexpected findings show that 5‐FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs.

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Rebound increase in microRNA levels at the end of 5-FU-based therapy in colorectal cancer patients

Cited by 4 publications

References 64 publications

Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential

Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential

How MicroRNAs Command the Battle against Cancer

5‐Fluorouracil treatment represses pseudouridine‐containing miRNA export into extracellular vesicles

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