Two Splice Variants of Y Chromosome-Located Lysine-Specific Demethylase 5D Have Distinct Function in Prostate Cancer Cell Line (DU-145)

One
of the major objectives of the Human Y Chromosome Proteome
Project is to characterize sets of proteins encoded from the human
Y chromosome. Lysine (K)-specific demethylase 5D (KDM5D) is located
on the AZFb region of the Y chromosome and encodes a JmjC-domain-containing
protein. KDM5D, the least well-documented member of the KDM5 family,
is capable of demethylating di- and trimethyl H3K4. In this study,
we detected two novel splice variants of KDM5D with lengths of 2650bp
and 2400bp that correspond to the 100 and 80 kDa proteins in the human
prostate cancer cell line, DU-145. The knockdown of two variants using
the short interfering RNA (siRNA) approach increased the growth rate
of prostate cancer cells and reduced cell apoptosis. To explore the
proteome pattern of the cells after KDM5D downregulation, we applied
a shotgun label-free quantitative proteomics approach. Of 820 proteins
present in all four replicates of two treatments, the abundance of
209 proteins changed significantly in response to KDM5D suppression.
Of these, there were 102 proteins observed to be less abundant and
107 more abundant in KDM5D knockdown cells compared with control cells.
The results revealed that KDM5D knockdown altered the abundance of
proteins involved in RNA processing, protein synthesis, apoptosis,
the cell cycle, and growth and proliferation. In conjunction, these
results provided new insights into the function of KDM5D and its splice
variants. The proteomics data are available at PRIDE with ProteomeXchange
identifier PXD000416.