In-depth analysis! RNA modification plays a key role in cancer development and progression!

May 27, 2020 /PRNewswire
BIOON/ -- Scientists from the University of Cambridge, Uk, discussthe key role of RNA modification in cancer in a recent review published in the international journal
nature reviewNature Reviews Cancerspecific modification of biological molecules is an effective method of regulating molecular function, a large number of downstream signaling pathways are affected by DNA and protein modification, many enzymes responsible for regulating protein and DNA modification are key targets of current cancer therapy, and epigenetics of RNA (i.ethe study of RNA modification) is a new research area, although although The RNA modifications of eukaryotes have been known since the 1970s, but it was only in the last decade that researchers discovered that most of them were identified and identified on transfer RNA and ribosome RNA, allowing researchers to perform a decotic analysis of identified mRNAs and multiplenon-coding RNAimage source: Barbieri, I et alNat Rev Cancer doi: 10.1038/s41568-020-0253-
2 Today there is growing evidence that RNA modification pathways are misregulated in human cancer, so it may be an ideal target for developing cancer therapies, the researchers report in this review, revealing the apnography pathways involved in cancer and its biology and its associated functionsCancer cells have a variety of characteristics that tend to give them unlimited growth and evade the host body's immune surveillance, eight different key features are defined as the main markers of cancer,the image abovereveals how RNA modified writers, readers, and erasures can inhibit these markers, and now researchers are increasingly aware that RNA modification and enzymes responsible for deposition, clarity and detection play a key role in different types of cancerIn some cases, a single enzyme often plays the opposite role in different cancer types, which is perhaps not surprising given the diversity of RNA modifications and the types of modified RNAs
; The A eraser (FTO) may have primitive carcinogenic properties, however, this may be explained by a large number of m6A-modified mRNAs, which is essential for maintaining high levels of expression for some original cancer-promoting mRNAs, whereas the removal of m6A may be necessary for the stability of a specifictumor suppressor mRNAs most RNA-modified molecules are characterized by the effects of cell autonomic markers, such as promoting the proliferation of cancer cells or mediating the invasive and metastasis potential of cancer cells; Researchers are likely to discover new noncellularly autonomous RNA modification-dependent functions, for example, where researchers are interested in studying the key role of RNA modification in the interaction between angiogenesis, cancer cells and the host immune system, studying the function of ADAR1 and FTO in regulating cell and systemic immune responses, or helping researchers use these enzymes as targets to broaden the effects of immunotherapy for cancer treatment recently, it has been cleared that the metabolic processes that cells experience in the course of cancer may be a central aspect of understanding the mechanisms of cancer progression, and scientists are now trying to find new ways to target cancer cell metabolism; however, researchers do not know the effects of RNA modification on cancer markers, but the pathways or as a new way to understand the mechanisms used to establish and regulate cancer metabolism, on the contrary, cancer metabolism changes may also have a potential direct impact on RNA modification and associated gene expression Studies have shown that RNA modification pathways regulate cell metabolism by regulating HIF1A mRNA, in particular, m6A-modified HIF1A can be stabilized by m6A modified and YTHDC2 combinations, while U34 oscillating tRNA modification can maintain high levels of HIF1 alpha in melanoma cells; Sensors for metabolites, such as METTL16 and FTO, are very sensitive to SAM levels, which in turn regulate SAM synthesis by modifying the SAM zylase gene MAT2A20, and similarly, FTO is very sensitive to alpha-ketone-pyridoxa, and it is inhibited by tumor 2-hydroxyglutanine Photo Source: Barbieri, I et al Nat Rev Cancer doi: 10.1038/s41568-020-0253-2
the challenges of the current cancer therapy development process when the treatment is tolerated, and tumors that first respond to specific anticancer drugs then develop acquired resistance and lead to tumor recurrence, such as the treatment of BRAFV6 This may be the case with BRAF inhibitors of melanoma driven by 00E, where in other cases the therapy tends to be only effective for a small number of patients, while the rest of the tumors exhibit primary resistance, and the use of immunotherapy to treat melanoma may be the case, although the treatment is more effective, but only half of tumors respond to the treatment Although RNA
epigenetic is still an undeveloped field, several studies have shown that RNA modification pathways can affect primary and acquired drug tolerance, FTO protects the effects of melanoma cell immunotherapy, and that its reduced activity increases the sensitivity of cancer cells to fight PD1 therapy; The immune response of the host body; more importantly, the inhibition of ADAR1 increases the sensitivity of melanoma cells to immunotherapy, and finally, the inactivation of the TRNA-modified enzymes of U34 oscillating tRNA modified enzymes increases the sensitivity of BRAFF600E-driven melanoma , and reverses the acquired resistance of cancer cells to BRAF inhibitors, the results of the study emphasize the development of targeted epigenetics of RNA
Characterized therapeutic preparations to increase the importance of current anticancer therapies Although multiple RNA modifications are mainly present in tRNA, the genetic inhibition of the associated enzymes seems to specifically affect cancer cells, but does not impair the survival of normal cells, which is well documented in the modifiers of tRNA U34 in cancer, tRNA modifications are usually present in tRNAs In subgroups, and its absence only affects the translation of subgroups of encoded transcripts, this specificity suggests that tRNA modification may be a more regulated phenomenon than previously thought, and these observational findings also suggest that the targeted tRNA modifier may be a viable option for future anticancer therapies many of the research evidence linking RNA epigenetic abnormalities to cancer strongly suggest that the development of inhibitors that target the rna pathways may be a productive choice and pursuit, and that the diversity of RNA modifications and the molecular pathways involved in RNA modification gives researchers hope, of course, that this is the beginning of the rna epigenetics cancer therapy (biovalleybioon.com) References: Barbieri, I., Kouzarides, T.
Role of RNA modifications in cancer
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Nat Rev Cancer
20, 303-322 (2020) doi:10.1038/s41568-020-0253-2