Non-small cell lung cancer (NSCLC) is the leading cause of cancer-induced deaths around the world, and platinum-based chemotherapy remains a standard-of-care for most patients with advanced NSCLC. DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. In this present study, we found that the level of p21 or RanBPM is lower in NSCLC than non-malignant tissues and has a highly positive correlation, which is negatively correlated with the survival of patients. We further revealed that RanBPM protein physically interacts with p21, RanBPM deubiquitinates p21 by recruiting a deubiquitinase USP11 to maintain protein stability of p21. Furthermore, RanBPM regulates DNA damage response (DDR) in a p21-dependent manner, and DNA damage promotes the translocation of RanBPM into the nucleus and regulates p21 protein stability through ATM-mediated pathways. We for the first time revealed a novel mechanism of p21 protein stability regulated by RanBPM, and the novel roles of RanBPM in the regulation of DDR.

Prostate cancer (PCa) is a top-incidence malignancy, and the second most common cause of death amongst American men and the fifth leading cause of cancer death in men around the world. Androgen receptor (AR), the key transcription factor, is critical for the progression of PCa by regulating a series of target genes by androgen stimulation. A number of co-regulators of AR, including co-activators or co-repressors, have been implicated in AR-mediated gene transcription and PCa progression. Epigenetic regulators, by modifying chromatin integrity and accessibility for transcription regulation without altering DNA sequences, influence the transcriptional activity of AR and further regulate the gene expression of AR target genes in determining cell fate, PCa progression and therapeutic response. In this review, we summarized the structural interaction of AR and epigenetic regulators including histone or DNA methylation, histone acetylation or non-coding RNA, and functional synergy in PCa progression. Importantly, epigenetic regulators have been validated as diagnostic markers and therapeutic targets. A series of epigenetic target drugs have been developed, and have demonstrated the potential to treat PCa alone or in combination with antiandrogens.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-induced deaths around the world, and platinum-based chemotherapy remains a standard-of-care for most patients with advanced NSCLC. DNA damage response (DDR) induced by platinum or Etoposide activated a panel of cell cycle-regulatory proteins including p21 through p53 pathway. In this present study, we found that the level of p21 or RanBPM is lower in NSCLC than non-malignant tissues and has a highly positive correlation, which is positively correlated with the survival of patients. We further revealed that RanBPM protein physically interacts with p21, RanBPM deubiquitinates p21 by recruiting a deubiquitinase USP11 to maintain protein stability of p21. Furthermore, RanBPM regulates DNA damage response (DDR) in a p21-dependent manner, and DNA damage promotes the translocation of RanBPM into the nucleus and regulates p21 protein stability through ATM-mediated pathways. We revealed a novel mechanism of p21 protein stability regulated by RanBPM, and the novel roles of RanBPM in the regulation of DDR.