The roles of LSD1-mediated epigenetic modifications in maintaining the pluripotency of bladder cancer stem cells.
Bladder cancer stem cells (BCSCs) may be the source for tumorigenesis, recurrence, and resistance to treatment of bladder carcinoma. Lysine-specific demethylase 1 (LSD1) plays crucial roles in the pluripotency maintenance of embryonic and cancer stem cells through the epigenetical modification of the associated genes, such as the regulation of bivalent domain at regulatory region of the developmental genes. It has also been found that LSD1 expression is elevated in clinical bladder cancer tissues compared with in normal tissues, and LSD1 knock down could significantly result in the suppression of bladder cancer cell line proliferation. Furthermore, results from our unpublished study showed that elevated levels of LSD1 are highly associated with the grades of the cancers, and more interestingly, LSD1 was mainly presented in the basal layer of bladder carcinoma tissue, co-localizing with BCSCs. Thus we hypothesized that LSD1 is mainly expressed in BCSCs in bladder cancer tissues, and LSD1-mediated epigenetic modification of the developmental genes may play important roles in maintaining pluripotency of BCSCs. LSD1 may become a reliable prognostic indicator and could serve as a molecular target in bladder cancer therapy.
Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
Weihua
W
Lan
Dianzheng
D
Zhang
Jun
J
Jiang
D014408:Biomarkers, Tumor / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D056466:Histone Demethylases / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D014408:Biomarkers, Tumor; D056466:Histone Demethylases; C495195:KDM1A protein, human