LGALS3 and AXIN1 gene variants playing role in the Wnt/ β-catenin signaling pathway are associated with mucinous component and tumor size in colorectal cancer

Abstract

The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/β-catenin pathway by binding to β-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the β-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9± 0.69 ng/ml vs. 0.79±0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/β-catenin pathway in the pathogenesis of colorectal cancer.

TET1 suppresses colon cancer proliferation by impairing β‐catenin signal pathway

“…[21][22][23] All of these indicate that cytosolic CTNNB1 degradation by the APC/Axin1 destruction complex represents a key step in the Wnt pathway. 24,25 It is worth noting that the aberrant activation of Wnt/β-catenin and its interaction with TCF will further transcribe some oncogenes expression in colon cancer. 26,27 The TCGA data analysis also reveals that the enhanced β-catenin/TCF responsive promoter activity is associated with insulin-like growth factor 1 receptor (IGF-1R) tyrosine kinase inhibitor sensitivity in human colon cancer, 28,29 which indicates that the upregulated β-catenin/TCF responsive promoter activity can be utilized as an index of therapy option.…”

“…While the WNT/β‐catenin signal can be activated when WNT‐seven‐pass transmembrane Frizzled (Fz)‐low‐density lipoprotein receptor‐related protein 6 complex is formed to inhibit the AXIN complex to degrade β‐catenin, all of these will lead to the β‐catenin stabilization, accumulation, and translocation to the nuclear to partner with T‐cell factor (TCF) to activate WNT targeting gene expression . All of these indicate that cytosolic CTNNB1 degradation by the APC/Axin1 destruction complex represents a key step in the Wnt pathway . It is worth noting that the aberrant activation of Wnt/β‐catenin and its interaction with TCF will further transcribe some oncogenes expression in colon cancer .…”

MicroRNA‐377 exerts a potent suppressive role in osteosarcoma through the involvement of the histone acetyltransferase 1‐mediated Wnt axis

“…It was observed that HAT1, a genetically encoded protein, negatively modulates the Wnt/βcatenin axis, which may be linked to mucus composition and the tumor size of colorectal cancer. The results suggest that HAT1 gene can regulate the Wnt/β-catenin axis (Korkmaz et al, 2016;Picco et al, 2017). With the purpose of investigating the upstream of differentially expressed gene (HAT1), we predicted the miRNA of HAT1 using the bioinformatics website and Venn map.…”

RNA sequencing of long-term label-retaining colon cancer stem cells identifies novel regulators of quiescence

“…In addition, several of the genes common to both the revSCs reported by Ayyaz et al. (2019) and qCSCs, namely, CLU ( Schepeler et al., 2007 ), CTSD ( Basu et al., 2019 ), CDKN1A ( Xu et al, 2016 ), EMP1 ( Yao et al, 2011 ), MUC3 ( Pai et al., 2016 ), LAMC2 ( Sánchez-Tilló et al., 2011 ), KRT19 ( Saha et al, 2017 ), LGALS3 ( Korkmaz et al, 2016 ), F3 ( Camps et al, 2020 ; Kinchen et al, 2018 ), ITGB4 ( Avvisato et al, 2007 ), CDH17 ( Wang et al, 2013 ), and GSN ( Shimura et al., 2004 ), are targets and/or regulators of Wnt signaling. Overall, these data demonstrate that both cycling and non-cycling CSCs share overlapping molecular profiles and further support the targeting of non-canonical hedgehog signaling to prevent disease relapse ( Buczacki et al, 2018 ; Regan, 2018 ; Regan et al, 2017 ).…”