Good news! Cancer is history (soon)!
"... In the study ... a team of scientists ... found that RNA plays a significant role in how DNA is packaged and stored in your cells, via a gene known as TET2 ...
This pathway also appears to explain a long-standing puzzle about why so many cancers and other disorders involve TET2-related mutations—and suggests a set of new targets for treatments. ...
With this lens, they turned their attention to a gene called TET2. For a long time, we’ve known that when TET2 or TET2-related genes are mutated, all sorts of problems follow. These mutations occur in 10-60% of different human leukemia cases, and pop up in other types of cancers as well. ...
The other members of the TET family act on DNA, so for years, researchers had been looking at TET2’s effects on DNA. But He’s lab found they’d been looking in the wrong place: TET2 actually affects RNA. ...
TET2 mutations also occur in a fraction of all adults older than 70 and contribute to an increased risk of heart disease, stroke, diabetes, and other inflammatory conditions, a condition known as CHIP. ..."
TET2 mutations also occur in a fraction of all adults older than 70 and contribute to an increased risk of heart disease, stroke, diabetes, and other inflammatory conditions, a condition known as CHIP. ..."
From the abstract:
"Mutation of tet methylcytosine dioxygenase 2 (encoded by TET2) drives myeloid malignancy initiation and progression. TET2 deficiency is known to cause a globally opened chromatin state and activation of genes contributing to aberrant haematopoietic stem cell self-renewal. However, the open chromatin observed in TET2-deficient mouse embryonic stem cells, leukaemic cells and haematopoietic stem and progenitor cells is inconsistent with the designated role of DNA 5-methylcytosine oxidation of TET2. Here we show that chromatin-associated retrotransposon RNA 5-methylcytosine (m5C) can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A (H2AK119ub) to promote an open chromatin state. TET2 oxidizes m5C and antagonizes this MBD6-dependent H2AK119ub deubiquitination. TET2 depletion thereby leads to globally decreased H2AK119ub, more open chromatin and increased transcription in stem cells. TET2-mutant human leukaemia becomes dependent on this gene activation pathway, with MBD6 depletion selectively blocking proliferation of TET2-mutant leukaemic cells and largely reversing the haematopoiesis defects caused by Tet2 loss in mouse models. Together, our findings reveal a chromatin regulation pathway by TET2 through retrotransposon RNA m5C oxidation and identify the downstream MBD6 protein as a feasible target for developing therapies specific against TET2 mutant malignancies."
UChicago scientists decode key mutation in many cancers (original news release) "Finding points to expanded role of RNA in human gene expression"
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