Overexpression of WDR79 in non‐small cell lung cancer is linked to tumour progression

Abstract

WD‐repeat protein 79 (WDR79), a member of the WD‐repeat protein family, acts as a scaffold protein, participating in telomerase assembly, Cajal body formation and DNA double‐strand break repair. Here, we first report that WDR79 is frequently overexpressed in cell lines and tissues derived from non‐small cell lung cancer (NSCLC). Knockdown of WDR79 significantly inhibited the proliferation of NSCLC cells in vitro and in vivo by inducing cell cycle arrest and apoptosis. WD‐repeat protein 79 ‐induced cell cycle arrest at the G0/G1 phase was associated with the expression of G0/G1‐related cyclins and cyclin‐dependent kinase complexes. We also provide evidence that WDR79 knockdown induces apoptosis via a mitochondrial pathway. Collectively, these results suggest that WDR79 is involved in the tumorigenesis of NSCLC and is a potential novel diagnostic marker and therapeutic target for NSCLC.

Expression of WDR79 is associated with TP53 mutation and poor prognosis in surgically resected non-small cell lung cancer

“…Recently, researchers also found that WDR79 may involve in increased risk for ER negative breast cancer 24. In NSCLC, WDR79 overexpression may involve in tumorigenesis, and in vitro study, Sun et al found that WDR79 promoted NSCLC cell proliferation 14, 29, 30. It was reported that WDR79 colocalized and interacted with USP7, which reduced the ubiquitination of Mdm2 and p53, and thereby increased the stability and extended the half-life of the two proteins 29.…”

“…What's more, WDR79 can regulate p53 protein expression via targeting p53 mRNA12, and WDR79 gene is regarded as a bidirectional gene partner to TP53 13. Sun et al found that overexpression of WDR79 is related with tumor progression in NSCLC 14. Another research in head and neck carcinomas demonstrated that WDR79 may accelerate the tumor occurrence and development 15.…”

Overexpression of the scaffold WD40 protein WRAP53β enhances the repair of and cell survival from DNA double-strand breaks

“…Although high levels of WRAP53 β , a scaffold protein involved in the intracellular trafficking of factors to Cajal bodies and DNA breaks, 3, 5, 29 are present in various cancers, 16, 17, 18, 19, 20 it remains unclear how such overexpression may alter its functions. Here we report that overexpression of WRAP53 β disturbs its recruitment and maintenance of factors to Cajal bodies, while at the same time enhancing the repair of DNA double-strand breaks.…”

“…16 WRAP53 β is also overexpressed in primary nasopharyngeal carcinoma, 17 esophageal squamous cell carcinoma, 18 non-small-cell lung cancer 19 and rectal cancer 20 and knockdown of this protein in cancer cells subsequently grafted into mice reduces the size of the tumors formed. 17, 19 In esophageal squamous cell carcinoma, overexpression of WRAP53 β was significantly correlated with tumor infiltration depth, clinical stage and lymph node metastasis. 18 However, for none of the studies mentioned above significant associations between WRAP53 β overexpression and patient survival were demonstrated.…”

WDR79 mediates the proliferation of non‐small cell lung cancer cells by regulating the stability of UHRF1

“…Emerging studies have shown that aberrations in WDR79 expression correlate with many different malignancies, such as rectal cancer,9 head and neck carcinomas,10 oesophageal squamous cell carcinoma,11 breast cancer,12 ovarian cancer 13 and nasopharyngeal carcinoma 14. Our previous studies revealed that WDR79 is frequently overexpressed in cell lines and tissues derived from non‐small cell lung cancer and promotes the proliferation of NSCLC cells,15, 16 which is consistent with a recent study 17. However, the underlying mechanism responsible for WDR79‐mediated NSCLC proliferation is not fully understood.…”