Argonaute Proteins Take Center Stage in Cancers

Nowak, Iwona; Sarshad, Aishe A.

doi:10.3390/cancers13040788

Cited by 16 publications

(13 citation statements)

References 127 publications

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“…In nasopharyngeal carcinoma, circMYC is reported to interact with miR-20b-5p and let-7e-5p simultaneously, which in turn target argonaute RISC component 1 (AGO1) and cryptochrome circadian regulator 2 (CRY2) ( 42 ). Both AGO1 and CRY2 tightly regulate cell development, proliferation and migration ( 49 , 50 ). Finally, circPVT1 binds to miR-497-5p through a specific binding site and affects its expression, leading to downregulation of miR-497-5p in HNSCC tumors with mutant p53 ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Circular RNAs are Potential Prognostic Markers of Head and Neck Squamous Cell Carcinoma: Findings of a Meta-Analysis Study

2022

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BackgroundSeveral studies have reported the role of circRNAs in the pathogenesis, diagnosis and prognosis of different cancers. This meta-analysis study aimed to evaluate the potential of using circRNAs as prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC).Methods816 relevant articles were retrieved from PubMed and Science Direct databases, out of which 17 met the inclusion criteria. These 17 studies were assessed for quality by the Newcastle-Ottawa Scale (NOS) system, and 9 high quality studies (NOS>7) were included in the meta-analysis. Cochran Q test and the I square (I2) metric were calculated to detect potential heterogeneity among studies. Sensitivity analysis was performed to validate the credibility of outcomes, and publication bias was determined using Begg’s funnel plot and Egger’s test. Hazard ratio (HR) and 95% Confidence Intervals (CIs) were used to evaluate overall survival (OS) of HNSCC patients by univariate and multivariate analyses.ResultsThe dysregulated levels of 9 circRNAs (circPVT1, circCORO1C, circ_0000199, circCUX1, circPARD3, circMYC, circ_0102272, circ_0092125 and circ_00072387) were inversely related to OS of HNSCC patients [upregulated circRNA (univariate analysis: HR = 3.40, 95% CI: 2.66-4.36, p < 0.0001, I2 = 0%; multivariate analysis: HR = 3.33, 95% CI: 2.54-4.38, p < 0.0001, I2 = 0%), downregulated circRNA (univariate analysis: HR = 2.83, 95% CI: 1.73-4.65, p < 0.0001, I2 = 57.8%; multivariate analysis: HR = 2.35, 95% CI: 1.42-3.89, p = 0.0009, I2 = 0%)]. The individual HR for these 9 circRNAs indicated inverse relation to OS, validating the overall HR. The dyregulated levels of these circRNAs were also associated with poor clinicopathological outcomes such as primary tumor size, lymph node metastasis, distant metastasis and poor tumor (T), nodes (N), metastases (M); i.e TNM staging, and six of these circRNAs regulated diverse micro RNAs, revealing their role in tumorigenesis and cancer progression.ConclusionNine different circRNAs dysregulated in HNSCC tumors may serve as potential prognostic markers of HNSCC. These markers are associated with reduced OS and poor clinicopathological outcomes of HNSCC patients. They are also involved in the pathogenesis and progression of HNSCC through diverse mechanisms.

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Section: Discussionmentioning

confidence: 99%

Circular RNAs are Potential Prognostic Markers of Head and Neck Squamous Cell Carcinoma: Findings of a Meta-Analysis Study

2022

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“…However, increased AGO2 mRNA levels were not associated with changes in total AGO2 protein levels using western blots in either cancer cell lines and miR-17 TG mice, implicating post-transcriptional regulation to stabilize protein levels. Silencing interactions of different miRNAs are dependent on and regulated by interactions with specific Argonaute proteins, with varying Argonaute protein ratios in different tissues [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Tracking miR-17-5p Levels following Expression of Seven Reported Target mRNAs

Qadir

Yang

et al. 2022

Cancers

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As the most prominent member of the miR-17-92 cluster, miR-17-5p is well associated with tumorigenesis and cancer progression. It can exert both oncogenic and tumor-suppressive functions by inducing translational repression and/or mRNA decay. The complexity of the tissue-specific expression of the targeted transcripts seems to contribute to the differential functions of miR-17-5p in different types of cancers. In this study, we selected 12 reported miR-17-5p targeting genes with mRNA levels unaffected by miR-17-5p expression and analyzed their expression in 31 organ tissues in transgenic mice by real-time PCR. Surprisingly, miR-17-5p expressing transgenic mice showed a positive correlation in these tissues between miR-17-5p expression levels and the selected miR-17-5p targeted transcripts; with high expression of the miRNA in organs with high selected miRNA-targeted mRNA levels. In cancer cell lines, overexpression of 7 reported miR-17-5p targeted genes’ 3′-UTRs promoted miR-17-5p expression; meanwhile, transfection of 3′-UTRs with mutations had no significant effect. Moreover, an increase in AGO2 mRNA was associated with 3′-UTR expression as confirmed by real-time PCR. Hence, miR-17-5p regulation by these target genes might be an alternative mechanism to maintain miR-17-5p expression at tissue-specific levels.

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“…Argonaute (AGO) proteins are loaded with small RNAs to silence complementary RNA transcripts, and they are central to RNAi. The dysregulated expression of the genes encoding AGO proteins was demonstrated in solid tumors as well as leukemia ( Nowak and Sarshad, 2021 ). The majority of reports agree that 3′-tRFs could be incorporated into AGO proteins and act through RNAi pathways ( Martinez et al, 2017 ).…”

Section: Reverse Transcription and Retrocopying By Reverse Transcript...mentioning

confidence: 99%

Transcriptional and reverse transcriptional regulation of host genes by human endogenous retroviruses in cancers

2022

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Human endogenous retroviruses (HERVs) originated from ancient retroviral infections of germline cells millions of years ago and have evolved as part of the host genome. HERVs not only retain the capacity as retroelements but also regulate host genes. The expansion of HERVs involves transcription by RNA polymerase II, reverse transcription, and re-integration into the host genome. Fast progress in deep sequencing and functional analysis has revealed the importance of domesticated copies of HERVs, including their regulatory sequences, transcripts, and proteins in normal cells. However, evidence also suggests the involvement of HERVs in the development and progression of many types of cancer. Here we summarize the current state of knowledge about the expression of HERVs, transcriptional regulation of host genes by HERVs, and the functions of HERVs in reverse transcription and gene editing with their reverse transcriptase.

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Argonaute Proteins Take Center Stage in Cancers

Cited by 16 publications

References 127 publications

Circular RNAs are Potential Prognostic Markers of Head and Neck Squamous Cell Carcinoma: Findings of a Meta-Analysis Study

Circular RNAs are Potential Prognostic Markers of Head and Neck Squamous Cell Carcinoma: Findings of a Meta-Analysis Study

Tracking miR-17-5p Levels following Expression of Seven Reported Target mRNAs

Transcriptional and reverse transcriptional regulation of host genes by human endogenous retroviruses in cancers

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