TROAP regulates cell cycle and promotes tumor progression through Wnt/β‐Catenin signaling pathway in glioma cells

Abstract

Aims Experimental evidence demonstrated a crucial role of TROAP (Trophinin‐associated protein) in regulating the cell proliferation of multiple tumors, while TROAP expression and function were largely unknown in glioma. We aimed to investigate the oncogenic role of TROAP and its potential mechanisms in gliomagenesis. Methods Four gene expression databases (GEO, TCGA, GTEx and CCLE) were enrolled in our study and used for TROAP expression and survival analysis. TROAP expression was quantified by qRT‐PCR, western blot and immunohistochemistry assays in glioma tissues and cell lines. TROAP knockdown and overexpression vector were constructed and transfected into glioma cells. CCK‐8, colony formation, transwell, and wound healing assays were used to evaluate cell viability, migration and invasion, flow cytometry to determine cell cycle arrest. Gene set enrichment analysis (GSEA) was conducted to screen the pathway involved in TROAP‐high phenotype. The expression of cell cycle and Wnt/β‐Catenin signaling proteins were analyzed by immunofluorescence and western blot. Results Based on the bioinformatic analysis and a series of functional assays, we found the TROAP was enriched in glioma tissues and cell lines, its overexpression was correlated with the clinicopathologic characteristics and poor prognosis. TROAP knockdown inhibited cell proliferation, migration, invasion, and G1/S cell cycle arrest compared with control group in glioma. Mechanism analysis revealed that TROAP activated Wnt/β‐Catenin pathway and upregulated its downstream targets expression, while silencing β‐Catenin or Axin2 could reverse the tumor‐promoting effects caused by TROAP, confirming that TROAP‐induced malignant phenotype and tumorigenesis via Wnt/β‐Catenin signaling pathway. Conclusion The present study found that TROAP accelerated the progression of gliomagenesis through Wnt/β‐Catenin pathway, and TROAP might be considered as a novel target for glioma therapy.

Downregulation of Methyltransferase-Like 14 Promotes Ovarian Cancer Cell Proliferation Through Stabilizing TROAP mRNA

“…Recently, Jing et al demonstrated that TROAP knockdown in gastric cancer cells results in reduced tumor cell growth, migration and invasion (36). Emerging evidence indicates that positive proliferation related gene, such as cyclin D1, survivin, and p-AKT, are positively regulated by TROAP (24)(25)(26). In the current study, we revealed TROAP as a downstream target of METTL14.…”

“…Although METTL14 overexpression decreased the proliferation of SKOV-3 cells (Figure 5E), the overexpression of TROAP reversed this inhibitory effect on cell proliferation in the SKOV-3 and A2780 cells (Figure 5E and Supplementary Figure S3). We next evaluated the expression of TROAP target genes, such as cyclin D1, survivin, and p-AKT, because their downregulation may also be involved in the inhibition of ovarian cancer cell proliferation due to METTL14 (24)(25)(26). As expected, the exogenous expression of METTL14 downregulated the expression levels of cyclin D1, survivin, and p-AKT.…”

Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review

“…Proteins such as heterochromatin, including cell surface protein, have a role in apoptosis. G1/S Progression search yielded two studies, one of which identified an important role of TROAP in cell cycle regulation and enhanced tumour progression [ 58 ]. Cell Cycle Progression search yielded 19 articles relevant to cell cycle progression.…”

Lithium attenuates blood–brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β‐catenin signaling‐dependent mechanism in mice

“…Upregulation of Wnt/β‐catenin might thus increase the risk of tumor generation or growth. It has been reported that Wnt/β‐catenin signaling plays an important role in prostate cancer and glioma, promoting self‐renewal or expansion 44,45 . In contrast, melanoma growth is slowed by the activation of Wnt/β‐catenin signaling 46 .…”

“…It has been reported that Wnt/β-catenin signaling plays an important role in prostate cancer and glioma, promoting self-renewal or expansion. 44,45 In contrast, melanoma growth is slowed by the activation 46 It is worth noting that although the role of Wnt/β-catenin signaling in tumor development is still controversial, tumor progression is a long-term process, in contrast to the acute onset of cerebral hemorrhage. In addition, Wnt/β-catenin signaling also plays an important role in vascular repair after traumatic brain injury.…”