GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer. Issue 4 (17th March 2020)

• Record Type: Journal Article
• Authors: Rong, Zeyin; Luo, Zai; Zhang, Jianming; Li, Tengfei; Zhu, Zhonglin; Yu, Zhilong; Fu, Zhongmao; Qiu, Zhengjun; Huang, Chen
• Is Part Of: Cancer science. Volume 111:Issue 4(2020)
• Page Start: 1203
• Page End: 1217
• Publication Date: 2020-03-17
• Subjects: biomarker -- colorectal cancer -- GINS4 -- growth -- KLF4; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14341
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: GINS complex subunit 4 (GINS4) is essential for DNA replication initiation and elongation in the G1 /S phase cell cycle in eukaryotes, however, its functional roles and molecular mechanisms remain unclear in many aspects. Our study was designed to investigate the clinical significance, biological function, and molecular mechanism of GINS4 in colorectal cancer (CRC). First, we confirmed that GINS4 expression was significantly overexpressed in CRC cells and tissues. The immunohistochemical results in tissue microarray from 106 CRC patients showed that a high level of GINS4 expression was positively correlated with advanced T stage, higher tumor TNM stage, and poor differentiation. The results from univariate and multivariate survival analysis models based on 106 CRC patients revealed that GINS4 might serve as an independent prognostic indicator for overall survival and disease‐free survival of CRC patients. Moreover, downregulated GINS4 can inhibit growth and the cell cycle and accelerate cell apoptosis progression in vitro as well as inhibit tumorigenesis in vivo. Besides, our results also indicated that Krüppel‐like factor 4 (KLF4) can negatively regulate GINS4 expression at the transcriptional level and the KLF/GINS4 pathway might play a vital role in the growth and prognosis of CRC. Abstract : Our research shows that Krüppel‐like factor 4/GINS complex subunit 4 (GINS4) signaling pathway could play important role in tumorigenesis and growth of human colorectal cancer (CRC). GINS4 could be an important predictor indicator for the prognosis of CRC patients.