Identification of WDR12 as a novel oncogene involved in hepatocellular carcinoma propagation

Abstract

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant cancer worldwide. Importantly, the precise mechanisms causing HCC pathogenicity are still unknown. The identification of potential oncogenes plays significant roles in finding novel therapeutic targets for human HCC.PurposeWDR12 (WD repeat protein 12), a member of WD repeats family, plays crucial roles in the ribosome biogenesis pathway. However, Whether WDR12 contributes to HCC development remains unknown. The objective of this study was to elucidate the role of WDR12 in HCC development.MethodsThe expression level of WDR12 in HCC tissues and adjacent non-tumor tissues were detected form Gene Expression Omnibus (GEO) database. The expression level of WDR12 in HCC cell lines were examined by RT-PCR and western blot. Kaplan-Meier analysis were used to analyze the effect of WDR12 level on overall and disease-free survival of HCC patients. To examine whether WDR12 supports development of HCC, we inhibited expression of WDR12 by using an shRNA-encoding lentivirus system. Effects of WDR12 knockdown were evaluated on cell-growth, cell-proliferation and cell-migration. The mechanisms involved in HCC cells growth, proliferation and migration were analyzed by western blot assay.ResultsIn silico analysis of HCC data sets showed that elevated expression of WDR12 correlated with high serum AFP level, high vascular invasion, high histologic grade and high TNM stage in HCC patients. Furthermore, up-regulated expression of WDR12 significantly correlated with the short overall survival and recurrence time of HCC patients. The shRNA-mediated knockdown of WDR12 expression resulted in reduced proliferation and migration of HepG2 and Huh-7 cells. Notably, inhibition of WDR12 resulted in decreased phosphorylation of AKT, mTOR and S6K1.ConclusionOur study indicates that WDR12 contributes to HCC propagation, and indicates that suppression of WDR12 may be a potential strategy for human HCC treatment.

Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells

“…The PLL3.7 lentiviral vector was used to express designed SH3BP5 shRNAs. Lentiviral production and cells infection were performed essentially as previous described [4,14]. For lentiviral production, HEK-293T cells were grown on 10-cm culture plates to ~90% confluence.…”

Rcl1 suppresses tumor progression of hepatocellular carcinoma: a comprehensive analysis of bioinformatics and in vitro experiments

“…Many studies have elucidated that many ribosome assembly factors could promote cell growth and metastasis in HCC by up-regulating the rate of ribosome biogenesis [9,[24][25][26][27][28]. But we found that RCL1 expression was commonly downregulated in HCC tissues and cell lines.…”

Biallelic Mutations in WDR12 is Associated With Male Infertility With Tapered-Head Sperm

“…As a member of PeBoW, endogenous WDR12 is a crucial factor for the processing of 32S precursor rRNA (ribosomal RNA), cell division, signal transduction, cell cycle progression, apoptosis, and cell proliferation (Rohrmoser, et al, 2007). Previous studies have suggested a role of WDR12 in myocardial infarction, coronary artery disease and Hepatocellular carcinoma (Yin, et al, 2018). High expression levels of WDR12 mRNA have been reported in the testis of adult mice.…”