CREBBP knockdown suppressed proliferation and promoted chemo-sensitivity via PERK-mediated unfolded protein response in ovarian cancer

Haoyang Hu; Sheng Yin; Ruyue Ma; Rujun Chen; Shuqing Li; Yaping Chen; He Fei; Lina Yang

doi:10.7150/jca.56135

CREBBP knockdown suppressed proliferation and promoted chemo-sensitivity via PERK-mediated unfolded protein response in ovarian cancer

J Cancer. 2021 Jun 1;12(15):4595-4603. doi: 10.7150/jca.56135. eCollection 2021.

Authors

Haoyang Hu¹, Sheng Yin², Ruyue Ma¹, Rujun Chen¹, Shuqing Li³, Yaping Chen¹, He Fei¹, Lina Yang¹

Affiliations

¹ Department of Obstetrics and Gynecology, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Shanghai, People's Republic of China.
² Department of Obstetrics and Gynecology, Zhongshan Hospital Fudan University, 180 Fenglin Road, Shanghai, People's Republic of China.
³ Obstetrics and Gynecology Hospital of Fudan University, 128 Shenyang Road, Shanghai, People's Republic of China.

Abstract

CREBBP, in short CBP, has been reported to be involved in tumorigenesis in various cancers, but its role in ovarian cancer remains largely unexplored. In our study, survival analysis of CBP in patients with ovarian cancer was conducted using the Kaplan-Meier Plotter database, then we utilized specific shRNA targeting CREBBP to block the expression of CBP, and detected its effect on cell proliferation and chemo-sensitivity in ovarian cancer cells. The results showed that high expression of CBP was correlated with poor prognosis in ovarian cancer patients. CREBBP knockdown in ovarian cancer cells significantly inhibited tumor proliferation both in vitro and in vivo. Moreover, CREBBP knockdown promoted chemo-sensitivity in ovarian cancer cells. Mechanism research further demonstrated that CREBBP knockdown attenuated unfolded protein response (UPR), which was mediated by PERK/ATF4/STC2 signaling pathway. Our research linked CBP and UPR in ovarian cancer and may provide new strategies for the clinical treatment of ovarian cancer.

Keywords: CREBBP; UPR; apoptosis; chemo-sensitivity; ovarian cancer.