Therefore, we hypothesize that TLX may contribute to NEPC acquisition by its suppression of AR and promote NEPC and PCSCs proliferation at least partially by its differential transcriptional regulation of CDKN1A and SIRT1. However, the specific role of TLX in NEPC progression and stemness of advanced prostate cancer need further investigation. The gene discussed is SIRT1; the disease is prostate cancer.