Overexpressed PLAGL2 transcriptionally activates Wnt6 and promotes cancer development in colorectal cancer

Abstract

Researchers hold the view that PLAGL2 is overexpressed in many malignancies and that it can promote tumor proliferation, migration, invasion and self-renewal; however, there is no evidence revealing a relationship between PLAGL2 and colorectal cancer (CRC). In the present study, genes that are overexpressed in CRC were screened using the COSMIC database and GEPIA database and the expression of PLAGL2 in carcinoma tissues and pericarcinomatous tissues was detected by RT-qPCR and western blot assays. A Cell Counting Kit-8 assay, a cell cycle analysis experiment and a xenograft model were used to explore the influence of PLAGL2 on CRC after knocking down PLAGL2 expression in HCT116 and SW480 cells. Using ChIP assays and Dual-Luciferase Reporter assays, the promoter regions to which PLAGL2 binds were discovered. It was observed that PLAGL2 was overexpressed in colorectal cancer and that it influenced the colorectal cancer cell cycle and promoted colorectal cancer proliferation in vivo and in vitro. The expression of some genes in the Wnt/β-catenin pathway, were downregulated after knocking down the expression of PLAGL2; Wnt6 was altered the most. PLAGL2 could bind to the promoter region of Wnt6 and promote its expression. These results indicated that PLAGL2 was overexpressed in CRC as a proto-oncogene and that it could active the Wnt/β-catenin pathway as a transcription factor by binding with the promoter region of Wnt6. PALGL2 was revealed to play an important role in colorectal cancer and may be a new therapeutic target for targeted medicine.

Circ-SOX4 drives the tumorigenesis and development of lung adenocarcinoma via sponging miR-1270 and modulating PLAGL2 to activate WNT signaling pathway

“…According to mechanism investigation, we confirmed that miR-1270 could interact with PLAGL2. PLAGL2 has been confirmed as an oncogene in colorectal cancer [47] and bladder urothelial The potential mRNAs that could bind with miR-1270 were searched from PITA, RNA22, miRmap and microT databases. c qRT-PCR examined the expressions of predicted mRNAs (PLAGL2, TCF12 and GLI3) in LUAD cell lines and normal human lung epithelial cell line.…”

Emerging Roles of Wnt Ligands in Human Colorectal Cancer

“…It is apparently upregulated during intestinal development and regeneration as well as in CRC cells (51,52). Overexpression or activation of Wnt6 could promote CRC development via activating the canonical Wnt signaling (53,54). Moreover, a significant upregulation of methylation in Wnt6 gene was also detected in CRC samples (109), and the Wnt6 rs6747776 polymorphism may participate in the increased risk of CRC associated with excessive saturated fat intake (110).…”

A novel molecular link between HOXA9 and WNT6 in glioblastoma identifies a subgroup of patients with particular poor prognosis

“…Although DNA methylation was clearly associated with WNT6 expression in glioma, this association was not universal. After ruling out the potential regulation of WNT6 by CAV1, UCA1 , and PLAGL2 in GBM (contrasting to what was previously described in gastric, bladder, and colorectal cancers (Fan et al , ; Li et al , ; Yuan et al , )), we showed that HOXA9, an oncogenic transcription factor whose expression has been associated with increased GBM aggressiveness (impacting on several hallmarks of cancer, increasing cell viability, migration, resistance to TMZ, and tumor growth in a subcutaneous mouse model, while decreasing mice OS in an orthotopic mouse model) and patients’ poor survival (Costa et al , ; Pojo et al , ), is one of the WNT6 transcriptional regulators in GBM (Fig. ), binding to its promoter region.…”