RNautophagic regulation of DNMT3a-dependent DNA methylation

Calorie restriction has long been known to extend lifespans and inhibit carcinogenesis in multiple species by slowing age-related epigenetic changes while the underlying mechanisms remain largely unknown. Herein, we found that starvation activated autophagy to remodel DNA methylation profile by inhibiting DNMT3a expression. Autophagy is impaired in chemoresistance which was associated with differential DNA methylation and could be reversed by DNMT3a inhibition. Autophagy activation decreases the expression of DNMT3a mRNA, accompanied with the downregulation of chemoresistance-related Linc00942. Knockdown of Linc00942 reduces DNMT3a expression and genome-wide DNA methylation while Linc00942 overexpression increased DNMT3a expression and correlated hypermethylation in cancer cells and primary tumor tissues. As a result, inhibition of autophagy increases Linc00942 expression to promote chemoresistance and autophagy activation or hypomethylating agent decitabine restores chemosensitivity by reducing global DNA methylation. The perfect prepared DNA was treated with Bisulfite from 27 samples, followed by whole genome amplification (WGA) and accomplished fragmentation processing. Then the assessment segues into array (or Chip) hybridization with the well-modified probe (> 850,000 sites, more than 95% CpG islands and 99% RefSeq genes coverage).