Ribavirin inhibits colorectal cancer growth by downregulating PRMT5 expression and H3R8me2s and H4R3me2s accumulation

Ge, Suyin; Zhang, Qingqing; Chen, Yonglin; Tian, Yizhen; Yang, Ruirui; Xu, Chen; Li, Fang; Zhang, Baolai

doi:10.1016/j.taap.2021.115450

Cited by 11 publications

(6 citation statements)

References 36 publications

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“…Several studies have supported the ability of PRMT5 to activate the transcriptional regulation of downstream molecules. A study by Ge et al [24] revealed that PRMT5 induces H4R3 symmetric dimethylation to increase the transcription of FGFR-3 and eIF4E. Liu et al [11] demonstrated that PRMT5-mediated H4R3me2s epigenetically repressed transcription of the c-Myc target genes, PTEN, p18, p21, p57, and p63, to promote cell proliferation and gastric cancer progression.…”

Section: Discussionmentioning

confidence: 99%

PRMT5 regulates cell pyroptosis by silencing CASP1 in multiple myeloma

et al. 2021

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Protein arginine methyltransferase 5 (PRMT5), a histone methyltransferase responsible for the symmetric dimethylation of histone H4 on Arg 3 (H4R3me2s), is an enzyme that participates in tumor cell progression in a variety of hematological malignancies. However, the biological functions of PRMT5 in multiple myeloma (MM) and the underlying molecular mechanisms remain unclear. In this study, we conducted a bioinformatics analysis and found that PRMT5 expression was significantly upregulated in MM. In vitro and in vivo phenotypic experiments revealed that knockdown of PRMT5 expression enhanced cell pyroptosis in MM. Moreover, we found that CASP1 expression was negatively correlated with PRMT5 expression, and repressing PRMT5 expression rescued both the phenotype and expression markers (N-GSDMD, IL-1b, and IL-18). Inhibition of PRMT5 activity increased CASP1 expression and promoted MM cell pyroptosis. Finally, high expression of PRMT5 or low expression of CASP1 was correlated with poor overall survival in MM. Collectively, our results provide a mechanism by which PRMT5 regulates cell pyroptosis by silencing CASP1 in MM.

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Section: Discussionmentioning

confidence: 99%

PRMT5 regulates cell pyroptosis by silencing CASP1 in multiple myeloma

et al. 2021

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“…The next day, mice were divided into four groups (n = 10/group) and treated with the intraperitoneal injection of vehicle (saline), ribavirin (100 mg/kg/ day), Doxorubicin (DOX, 1.5 mg/kg/3 day), or ribavirin + DOX. According to recent studies using ribavirin in glioblastoma and colorectal cancer, 29,30 we determined that 100 mg/kg of body weight (BW) per day in mice were appropriate doses, and this dosage is considered completely safe. 33 On Day 12, the mice were killed by cervical dislocation following etherinhalation anaesthesia.…”

Section: Allograft Tumour Modelmentioning

confidence: 99%

“…Ribavirin, a broad‐spectrum antiviral agent, targets the inosine monophosphate (IMP) dehydrogenase, thus inhibiting the biosynthesis of viral mRNA through an effect on the GMP, GDP and GTP 24–27 . Emerging evidence has revealed that ribavirin shows anti‐tumour effect in numerous types of cancers, such as glioblastoma, colorectal carcinoma and breast cancer 28–30 . However, its exact mechanism of action in tumour cells has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…[24][25][26][27] Emerging evidence has revealed that ribavirin shows anti-tumour effect in numerous types of cancers, such as glioblastoma, colorectal carcinoma and breast cancer. [28][29][30] However, its exact mechanism of action in tumour cells has not been fully elucidated. Here, we described the anti-tumour efficacy of ribavirin in soft tissue sarcomas (STS), a potent, both type I PRMTs and type II PRMT5 inhibitor.…”

Section: Introductionmentioning

confidence: 99%

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Ribavirin inhibits cell proliferation and metastasis and prolongs survival in soft tissue sarcomas by downregulating both protein arginine methyltransferases 1 and 5

Zhang

Yang

Tian

et al. 2022

Basic Clin Pharma Tox

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Protein arginine methyltransferases 1 and 5 (PRMT1 and PRMT5) are frequently overexpressed in diverse types of cancers and correlate with poor prognosis, thus making these enzymes potential therapeutic targets. The aim of this study was to assess and elucidate the anti-tumour effect and epigenetic regulatory mechanism of ribavirin in soft tissue sarcomas (STS). We showed that ribavirin inhibited growth and metastasis and prolonged survival in animals bearing STS cells by downregulating the mRNA and protein levels of PRMT1/PRMT5 and attenuating the accumulation of asymmetric and symmetric di-methylation of arginine (ADMA and SDMA). Furthermore, ribavirin lowered the permeability of the peritoneum in KM mice bearing S180 ascites via decreasing the level of vascular endothelial growth factor (VEGF). Ribavirin was a potent inhibitor of cell proliferation and metastasis in STS cells through downregulation of both type I PRMT1 and type II PRMT5. Ribavirin could be used to enhance the efficacy of doxorubicin in STS allograft tumour models.

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“…Studies had shown that targeting MUC1-C by GO-203 can inhibit the AKT-S6K-eIF4A pathway and block the proliferation and survival of CRC cells ( 66 ). Overexpression of eIF4e was reported to associated with poor prognosis in CRC patients ( 67 , 68 ).…”

Section: Eukaryotic Translation Initiation Factorsmentioning

confidence: 99%

The progress of protein synthesis factors eIFs, eEFs and eRFs in inflammatory bowel disease and colorectal cancer pathogenesis

et al. 2022

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Colorectal diseases are threatening human health, especially inflammatory bowel disease (IBD) and colorectal cancer (CRC). IBD is a group of chronic, recurrent and incurable disease, which may affect the entire gastrointestinal tract, increasing the risk of CRC. Eukaryotic gene expression is a complicated process, which is mainly regulated at the level of gene transcription and mRNA translation. Protein translation in tissue is associated with a sequence of steps, including initiation, elongation, termination and recycling. Abnormal regulation of gene expression is the key to the pathogenesis of CRC. In the early stages of cancer, it is vital to identify new diagnostic and therapeutic targets and biomarkers. This review presented current knowledge on aberrant expression of eIFs, eEFs and eRFs in colorectal diseases. The current findings of protein synthesis on colorectal pathogenesis showed that eIFs, eEFs and eRFs may be potential targets for CRC treatment.

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Ribavirin inhibits colorectal cancer growth by downregulating PRMT5 expression and H3R8me2s and H4R3me2s accumulation

Cited by 11 publications

References 36 publications

PRMT5 regulates cell pyroptosis by silencing CASP1 in multiple myeloma

PRMT5 regulates cell pyroptosis by silencing CASP1 in multiple myeloma

Ribavirin inhibits cell proliferation and metastasis and prolongs survival in soft tissue sarcomas by downregulating both protein arginine methyltransferases 1 and 5

The progress of protein synthesis factors eIFs, eEFs and eRFs in inflammatory bowel disease and colorectal cancer pathogenesis

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