The epitranscriptome: At the crossroad of cancer prognosis

Fazio, Pietro Di

doi:10.1016/j.ebiom.2021.103231

Cited by 3 publications

(3 citation statements)

References 8 publications

(7 reference statements)

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“…The cancer-associated epitranscriptome provides a new perspective in deciphering tumor progression. Dynamic RNA modifications involve the crosstalk among writers, erasers, and readers [39]. The most prevalent mRNA modification, N 6 -methyladenosine (m 6 A), affects the stability and translation of key oncogenic transcripts.…”

Section: Fra-1 Structure and Regulationmentioning

confidence: 99%

FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer

Casalino,

Talotta,

Matino

et al. 2023

IJMS

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Among FOS-related components of the dimeric AP-1 transcription factor, the oncoprotein FRA-1 (encoded by FOSL1) is a key regulator of invasion and metastasis. The well-established FRA-1 pro-invasive activity in breast cancer, in which FOSL1 is overexpressed in the TNBC (Triple Negative Breast Cancer)/basal subtypes, correlates with the FRA-1-dependent transcriptional regulation of EMT (Epithelial-to-Mesenchymal Transition). After summarizing the major findings on FRA-1 in breast cancer invasiveness, we discuss the FRA-1 mechanistic links with EMT and cancer cell stemness, mediated by transcriptional and posttranscriptional interactions between FOSL1/FRA-1 and EMT-regulating transcription factors, miRNAs, RNA binding proteins and cytokines, along with other target genes involved in EMT. In addition to the FRA-1/AP-1 effects on the architecture of target promoters, we discuss the diagnostic and prognostic significance of the EMT-related FRA-1 transcriptome, along with therapeutic implications. Finally, we consider several novel perspectives regarding the less explored roles of FRA-1 in the tumor microenvironment and in control of the recently characterized hybrid EMT correlated with cancer cell plasticity, stemness, and metastatic potential. We will also examine the application of emerging technologies, such as single-cell analyses, along with animal models of TNBC and tumor-derived CTCs and PDXs (Circulating Tumor Cells and Patient-Derived Xenografts) for studying the FRA-1-mediated mechanisms in in vivo systems of EMT and metastasis.

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Section: Fra-1 Structure and Regulationmentioning

confidence: 99%

FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer

Casalino,

Talotta,

Matino

et al. 2023

IJMS

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“… 4 Post‐transcriptional modification at the RNA level, known as epitranscriptome, has gained increasing attention because of its extensive role in tumor progression. 5 N1‐methyladenosine (m1A) is a RNA methylation modification. Although the prevalence of m1A is lower than that of m6A, its effects on the structure and function of RNA are stronger in comparison to that of m6A, due to the presence of an additional positive charge in the modified nitrogen.…”

Section: Introductionmentioning

confidence: 99%

“…Metastasis is accompanied by a series of genetic and epigenetic molecular events 4 . Post‐transcriptional modification at the RNA level, known as epitranscriptome, has gained increasing attention because of its extensive role in tumor progression 5 . N1‐methyladenosine (m1A) is a RNA methylation modification.…”

Section: Introductionmentioning

confidence: 99%

MFAP2, upregulated by m1A methylation, promotes colorectal cancer invasiveness via CLK3

Xue

Zhang

et al. 2022

Cancer Medicine

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Background: Distant metastasis is the main cause of mortality in colorectal cancer (CRC) patients. N1-methyladenosine (m1A) is a type of epitranscriptome modification. While its regulatory effect on mRNA and its role in CRC metastasis remain unclear. Methods: The m1A methylation profile of mRNAs in CRC was revealed by m1A methylated RNA immunoprecipitation sequencing. The expression of MFAP2 in tumor tissues was measured by immunohistochemistry and then correlated with the clinical characteristics and prognosis of CRC patients. The role of MFAP2 in the invasiveness of CRC cells was evaluated by transwell assays and peritoneal metastatic model in nude mice. The downstream targets of MFAP2 was screened by mass spectrometry analysis. Then the role of MFAP2-CLK3 signaling axis was verified by cotransfecting MFAP2 siRNA and CLK3 plasmid in CRC cells.Results: Microfibril associated protein 2 (MFAP2) mRNA was overexpressed and m1A-hypermethylated in CRC. High expression of MFAP2 was closely related to lymph node metastasis and distant metastasis, leading to poor prognosis in patients with CRC. In vivo and in vitro studies showed that silencing of MFAP2 inhibited the migration, invasion and metastasis of CRC cells. CDC Like Kinase 3 (CLK3) was a potential downstream target of MFAP2. Further studies showed that MFAP2 depletion might induce autophagic degradation of CLK3, and the role of MFAP2 in the invasiveness of CRC cells was dependent on CLK3. Conclusions:Our results uncover a newly identified MFAP2-CLK3 signaling axis, which is a potential therapeutic target for CRC metastasis.

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