GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

Abstract

| 1203 wileyonlinelibrary.com/journal/cas | INTRODUC TI ONColorectal cancer is the third most common tumor and the third leading cause of cancer-related death in man and women in the world. 1,2 In China, there was an increase of over 376 300 cases of CRC and a total of 191 000 deaths during 2015. 3 Environmental and lifestyle changes, including an altered diet, lack of appropriate physical activity, circadian disruption, and increase in alcohol consumption, have enormously aggravated the burden of CRC. 4 In the past several years, the incidence and mortality of CRC increased rapidly and the onset age was muchThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractGINS complex subunit 4 (GINS4) is essential for DNA replication initiation and elongation in the G 1 /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. K E Y W O R D Sbiomarker, colorectal cancer, GINS4, growth, KLF4

<p>Bioinformatics Analysis Identifies a Novel Role of <em>GINS1</em> Gene in Colorectal Cancer</p>

“…Moreover, GINS4 overexpression associated with poor prognosis of CRC patients, whereas downregulation of GINS4 inhibited growth and cell cycle in vitro, accelerated apoptosis, and suppressed tumorigenesis in vivo. 23 Xiaoli reported that GINS3 expression was higher in CRC than in adjacent normal tissues based on qRT-PCR experiments of 137 consecutive samples. The study also revealed that GINS3 expression was correlated with poor overall survival and disease-free survival of CRC patients.…”

Differential Expression Profiles of Long Noncoding RNA and mRNA in Dexamethasone-Induced Apoptosis of Human Bone Marrow Mesenchymal Stem Cells

“…GINS4, also known as SLD5, is an important player in the initial stages of DNA replication. Down-regulation of GINS4 promoted cell cycle arrest, growth inhibition, and apoptosis in colorectal cancer cells [32]. Inactivation of CIT, a serine/threonine kinase, increased apoptosis, suppressed proliferation, and arrested cell cycle via the regulation of Cyclophilin A in PDAC cells [33].…”

“…In particular, an interaction network was identi ed from lncRNA (XLOC_011523) to mRNA (CDKN3, E2F7, and IQGAP3), involving 21 mRNA and 8 lncRNA. Moreover, some key mRNA were identi ed, such as GINS4, CIT, CDK1, SAMHD1, and CDH11, which were reported to be closely associated with the regulation of cell proliferation and apoptosis [32][33][34][35][36].…”

Differential expression profiles of long noncoding RNAs and mRNAs in human bone marrow mesenchymal stem cells after exposure to a high-dosage of dexamethasone

“…In particular, an interaction network was identi ed between the lncRNAs (XLOC_011523) and mRNAs (CDKN3, E2F7, and IQGAP3), which involved 21 mRNAs and 8 lncRNAs. Moreover, some key mRNAs, such as GINS4, CIT, CDK1, SAMHD1, and CDH11, were identi ed have been reported to be closely associated with the regulation of cell proliferation and apoptosis [37][38][39][40][41].…”

“…GINS4, also known as SLD5, plays an important role in the initial stages of DNA replication. Downregulation of GINS4 promoted cell cycle arrest, growth inhibition, and apoptosis in colorectal cancer cells [37].…”