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Purpose: The overexpression and knockdown of PLK4 were both reported to generate aneuploidy. Thus, we aimed to investigate whether genetic variants in PLK4 contribute to the development of hepatocellular carcinoma (HCC). Methods: We evaluated associations of common variants in PLK4 and its promoter for the risk of HCC in our association study (1300 cases and 1344 controls). The genotype‐tissue expression (GTEx) and The cancer genome atlas (TCGA) databases were used to quantify the expression of PLK4. Cell proliferation and migration affected by PLK4 in HCC were assessed in vitro. Drug susceptibility testing (DST) model was used to assess the sensibility of PLK4‐activated HCC to CFI‐400945, a small molecule inhibitor of PLK4. Results: Herein, we found a significant association between rs3811741, located in the PLK4 intron, and liver cancer risk (OR = 1.26, P = 9.81 × 10−5). Although PLK4 expressed at lower levels in somatic tissues compared to the testis, the risk allele A of rs3811741 was associated with increased PLK4 expression in liver cancer tissues. Additionally, PLK4 high expression was remarkably associated with shortened survival of HCC (HR = 1.97, P = .001). Furthermore, overexpression of PLK4 promoted, while knockdown of PLK4 suppressed cancer cell proliferation, migration, and invasion. DST model demonstrated that CFI‐400945 can effectively suppress rampant proliferation of HCC with highly expressed PLK4. Conclusion: Taken together, our study demonstrated that PLK4 is a susceptibility gene and plays an oncogenic role in HCC. Furthermore, we identified that PLK4 sensitives HCC to CFI‐400945, which may be an ideal therapy target for HCC. [ABSTRACT FROM AUTHOR]

Background: Accompanied by HBV infection, HBV mutations gradually occur because HBV polymerase appears proofread deficiencies. In our previous study, we have identified that EnhII/BCP/PC mutations and genotype C of HBV DNA were associated with hepatocellular carcinoma (HCC) risk. In this study, we extend our research to explore HCC prognosis associated genotype and mutations in EnhII/BCP/PC regions. Methods: We designed a case‐cohort study of 331 HCC patients to evaluate the effects of the HBV genotypes and mutations on HCC survival. Log‐rank test and Cox proportional hazard models were used for the analyses. Results: Results showed that genotype C, which was more frequent in HBV‐related HCC (77.4%), presented a negative signal with HCC survival. Interestingly, we detected a significant association between EnhII/BCP/PC mutation nt1753 and HCC prognosis (Log‐rank P = 0.034). Subgroup analysis revealed that this risk effect was more pronounced in non‐B genotype (P = 0.090 for heterogeneity test). We also detected a borderline multiplicative interaction between genotypes of nt1753 and HBV genotype on HCC survival (P for interaction = 0.069). Conclusions: These findings indicated that, in Chinese population, nt1753 in EnhII/BCP/PC region might be a novel marker for HCC prognosis. [ABSTRACT FROM AUTHOR]

Our previous work demonstrated cancer‐testis (CT) genes as a new source of candidate driver of cancer. Recently, mounting evidence indicates that long noncoding RNAs (lncRNAs) with CT expression pattern could play a pivotal role in cancer biology. Here, we characterized a conserved CT long noncoding RNA (CT‐lncRNA), PCAT6, which is expressed exclusively in the testis and is reactivated in liver hepatocellular carcinoma (LIHC) tissues due to the highly frequent amplification. The expression in LIHC was correlated with clinical prognosis in TCGA data. Knockdown of PCAT6 could inhibit cell proliferation and migration in hepatocellular carcinoma (LIHC) cells. Gene set enrichment analysis (GSEA) based on coexpression network revealed that PCAT6 was involved in similar cilium‐related pathways in the testis and LIHC tissues. However, PCAT6 was mainly positively correlated with gametogenesis‐related pathways in the testis but was coexpressed with mitotic cell cycle genes in LIHC. Together, our data demonstrated that CT‐lncRNA PCAT6 represents the similarity and difference between tumorigenesis and gametogenesis. The CT expression pattern and important role in LIHC oncogenesis make PCAT6 an ideal target for LIHC diagnosis and therapy. [ABSTRACT FROM AUTHOR]