ZKSCAN3 promotes ovarian cancer cell proliferation through upregulating HSPB1
Ovarian cancer has the worst prognosis in major gynecological cancers. Current therapies includes platinum, taxol, angiogenesis inhibitor, PARP inhibitor. However, most ovarian cancer patients develop resistance. Identification of more pro-tumor factors in ovarian cancer may shed insight into ovarian cancer biology and therapy. In this study, we find ZKSCAN3, a zinc-finger transcription factor is overexpressed in ovarian cancer. We show ZKSCAN3 promotes ovarian cancer cell proliferation. Through RNA-sequencing and ChIP-sequencing, HSPB1 is identified as a target gene of ZKSCAN3. HSPB1 expression is significantly decreased by suppressing ZKSCAN3. Suppressing HSPB1 expression inhibits ovarian cancer cell proliferation as well. In contrast, expressing exogenous HSPB1 partially rescues the cell proliferation in ZKSCAN3 knock-down cells. Collectively, our study uncovers a functional ZKSCAN3-HSPB1 axis that promotes ovarian cancer cell proliferation. Overall design: To examine the effect on transcriptome by ZKSCAN3, we performed ChIP-Seq and RNA-Seq to identify ZKSCAN3 directly-regulated genes. For ChIP-Seq, we stably expressed HA-ZKSCAN3 in Hey ovarian cancer cells. HA antibody was used for Chromatin IP. ChIP DNA was analyzed with Next generation sequencing. For RNA-Seq, Hey cells were transduced with lentiviruses expressing ZKSCAN3-shRNA or control sequences. Total RNA was extracted for RNA-Seq.