ESR1 and breast cancer: Similarly, piR-823 has been shown to be upregulated in breast cancer cells and enhance the expression of stem cell regulators (OCT4, SOX2, KLF4, NANOG, h-TERT) and methyltransferases (DNMT1, DNMT3A, DNMT3B), thereby promoting the hypermethylation of the adenomatous polyposis coli (APC) promoter, activating Wnt signaling, and driving tumor growth—whereas piR-823 knockdown, which also increases ERα and decreases h-TERT expression via the inhibition of the PI3K/Akt/mTOR pathway, suppresses cancer cell proliferation [159,160].