The RNA binding protein QKI5 suppresses ovarian cancer via downregulating transcriptional coactivator TAZ

Tao Liu; Yu Yang; Zhe Xie; Qingya Luo; Dan Yang; Xiaoyi Liu; Hongyan Zhao; Qinglv Wei; Yi Liu; Lanfang Li; Yuya Wang; Fang Wang; Jianhua Yu; Jing Xu; Jia Yu; Ping Yi

doi:10.1016/j.omtn.2021.07.012

The RNA binding protein QKI5 suppresses ovarian cancer via downregulating transcriptional coactivator TAZ

Mol Ther Nucleic Acids. 2021 Jul 29:26:388-400. doi: 10.1016/j.omtn.2021.07.012. eCollection 2021 Dec 3.

Authors

Tao Liu¹, Yu Yang¹, Zhe Xie², Qingya Luo³, Dan Yang¹, Xiaoyi Liu¹, Hongyan Zhao^{1

4}, Qinglv Wei¹, Yi Liu¹, Lanfang Li², Yuya Wang¹, Fang Wang⁵, Jianhua Yu⁶, Jing Xu¹, Jia Yu⁵, Ping Yi¹

Affiliations

¹ Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China.
² Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China.
³ Department of Pathology, The First Affiliated Hospital of Army Medical University, Chongqing 400038, China.
⁴ School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China.
⁵ Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
⁶ Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.

Abstract

RNA-binding proteins (RBPs) are a set of proteins involved in many steps of post-transcriptional regulation to maintain cellular homeostasis. Ovarian cancer (OC) is the most deadly gynecological cancer, but the roles of RBPs in OC are not fully understood. Here, we reported that the RBP QKI5 was significantly negatively correlated with aggressive tumor stage and worse prognosis in serous OC patients. QKI5 could suppress the growth and metastasis of OC cells both in vitro and in vivo. Transcriptome analysis showed that QKI5 negatively regulated the expression of the transcriptional coactivator TAZ and its downstream targets (e.g., CTGF and CYR61). Mechanistically, QKI5 bound to TAZ mRNA and recruited EDC4, thus decreasing the stability of TAZ mRNA. Functionally, TAZ was involved in the QKI5-mediated tumor suppression of OC cells, and QKI5 expression was inversely correlated with TAZ, CTGF, and CYR61 expression in OC patients. Together, our study indicates that QKI5 plays a tumor-suppressive role and negatively regulates TAZ expression in OC.

Keywords: QKI5; RBP; TAZ; ovarian cancer; post-transcriptional control.