**Conflict of interest**

The authors declare no conflict of interest.

*Epigenetics and DNA Repair in Cancer DOI: http://dx.doi.org/10.5772/intechopen.94030*

*DNA - Damages and Repair Mechanisms*

L-OHP (oxaliplatin) [127].

**7. Conclusions**

cancer response.

**Acknowledgements**

**Conflict of interest**

Thanks to IntechOpen.

The authors declare no conflict of interest.

by promoting HR repair, implying an oncogenic role for METTL3 and m6A. At the same time, FTO becomes a promising target to develop FTO inhibitors like Rhein,

Hepatocarcinogenesis is correlated with abnormal m6A modifications, high METTL3 and YTHDF1 expression in hepatocellular carcinoma (HCC) is associated with poor prognosis, with its combination as a malignant marker, according to Zhou et al. [123]. The participation of the machinery regulating m6A was clarified by the work of Chen et al. [124]. They found a significant increase in mRNA m6A levels, supporting the role of m6A in liver cancers. When METTL3 is downregulated, it is unable to act on tumor suppressor SOCS2, being silenced by METTL3 through m6A-YTHDF2. SOCS2 transcripts are a direct target of YTHDF2 with mediated mRNA decay, promoting tumor progression. Recently, Lin et al. [125] found that METTL3 depletion leads to a resistant phenotype in HCC with sorafenib treatment through regulation of FOXO3 expression. FOXO3 m6A methylation maintains stability, but its absence accelerates degradation. The modification is read by YTHDF1, which stabilizes m6A-labeled RNA and promotes protein synthesis. These results contrast with those obtained by Taketo and colleagues [126] when they established a METTL3-KD using a pancreatic adenocarcinoma cell line. The authors concluded that these cells had higher sensitivity to gemcitabine, 5-fluorouracil, cisplatin, and irradiation. It is clear that METTL3 plays a key role in resistance to therapy, but the way this gene behaves in different types of cancer is not yet understood. In a study on colorectal cancer (CRC), it was found that c-Myc activates the YTHDF1 gene expression. YTHDF1 is overexpressed in CRC and has been associated with lymph node metastasis and poor prognosis, as the evidence in vitro with YTHDF1 knockdown indicates that cancer cells are sensitized to the exposure of 5-Fluorouracil and

The SWI/SNF complex has been shown to be a central regulator in DNA repair, over other epigenetic complexes such as Polycomb repressive complex 1 (PRC1) and 2 (PRC2), which require the cooperation of their subunits and epigenetic markers to trigger the on–off signaling cascade, generated by acetylation, methylation, or ubiquitination of genes involved in response to DNA damage. We see that participation of epigenetics in the cellular responses goes far beyond DNA promoter methylation and histone modification. Methylation of RNA has a critical role in cell maintenance, changing our notion about RNA functions. We do not know whether deregulation of the m6A machinery could result in cancer development or progression by altering DNA damage response, but knowledge of molecular mechanisms of regulation of m6A cellular modification in tumor cells may develop a combined therapy for m6A regulator proteins as targets that facilitate a better

Meclofenamic acid (MA2), or its ethyl ester form, MA2 [122].

**178**
