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Published on: January 12, 2020
ZKSCAN3 promotes ovarian cancer cell proliferation by increasing HSPB1 expression
Qian Ke1, Zhenyong Li1, Li Fan2
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Ovarian cancer has the worst prognosis among major gynecological cancers. Current therapies include platinum, Taxol, angiogenesis inhibitors, and poly[ADP-ribose]polymerase (PARP) inhibitors. However, resistance develops in most ovarian cancer patients. Identification of more pro-tumor factors in ovarian cancer may provide insights into ovarian cancer biology and therapy. In this study, we find ZKSCAN3, a zinc-finger transcription factor, is overexpressed in ovarian cancer. We show that ZKSCAN3 promotes ovarian cancer cell proliferation. Through RNA-Seq and chromatin immunoprecipitation (ChIP)-seq, HSPB1 is identified as a target gene of ZKSCAN3. HSPB1 expression is significantly decreased upon suppressing ZKSCAN3 expression. Suppressing HSPB1 expression also inhibits ovarian cancer cell proliferation. In contrast, expressing exogenous HSPB1 partially rescues the cell proliferation in ZKSCAN3 knockdown cells, which supports HSPB1 as a functional target gene of ZKSCAN3. Collectively, our study uncovers a functional ZKSCAN3-HSPB1 axis that promotes ovarian cancer cell proliferation.
Insights
This study identifies ZKSCAN3 as a key factor overexpressed in ovarian cancer, promoting tumor cell growth. The ZKSCAN3-HSPB1 axis is a novel target for ovarian cancer therapy.
Area of Science:
- Gynecologic Oncology
- Cancer Biology
- Molecular Oncology
Background:
- Ovarian cancer presents a poor prognosis among gynecological malignancies.
- Current treatments like platinum, Taxol, and PARP inhibitors face challenges due to resistance.
- Identifying novel pro-tumor factors is crucial for advancing ovarian cancer understanding and treatment.
Purpose of the Study:
- To investigate the role of ZKSCAN3, a zinc-finger transcription factor, in ovarian cancer.
- To identify downstream targets of ZKSCAN3 that contribute to ovarian cancer progression.
- To elucidate the functional ZKSCAN3-HSPB1 signaling pathway in ovarian cancer.
Main Methods:
- Overexpression analysis of ZKSCAN3 in ovarian cancer tissues.
- RNA-sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to identify ZKSCAN3 targets.
- Functional assays including gene knockdown and rescue experiments to assess proliferation.
Main Results:
- ZKSCAN3 is significantly overexpressed in ovarian cancer and promotes cell proliferation.
- HSPB1 is identified as a direct transcriptional target of ZKSCAN3.
- Suppression of HSPB1 inhibits proliferation, while its overexpression rescues proliferation in ZKSCAN3-depleted cells.
Conclusions:
- ZKSCAN3 acts as an oncogene in ovarian cancer by promoting cell proliferation.
- The ZKSCAN3-HSPB1 axis represents a novel molecular mechanism driving ovarian cancer growth.
- Targeting the ZKSCAN3-HSPB1 pathway may offer new therapeutic strategies for ovarian cancer.
