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Background: Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors. Long noncoding RNAs play critical roles in tumorigenesis. Methods: Real‐time quantitative PCR arrays were used to evaluate the expression levels of cytoskeleton regulator RNA (CYTOR) in NPC tissues and cells. Cell counting kit‐8 and colony formation analyses were used to test the NPC cell viability, while wound healing and transwell assays were employed to detect cell invasion and migration ability. Luciferase reporter assay and Western blot analyses were employed to explore the relationships among CYTOR, miR‐613, and ANXA2. Results: We found that CYTOR expression was elevated both in NPC tissues and cells. Functional assays revealed that CYTOR promoted the invasion and migration of NPC cells. The established spontaneous lymph node metastasis model also confirmed that CYTOR promoted NPC cell metastasis in vivo. Mechanically, we found that the subcellular localization of CYTOR mostly occurred in the cell cytoplasm. Luciferase reporter and RIP assays confirmed that CYTOR functioned as the molecular sponge of miR‐613. Subsequent experiments confirmed that ANXA2 was directly targeted by miR‐613. Gain‐ and loss‐of‐function studies further confirmed that CYTOR induced the upregulation of ANXA2 by competitively binding to miR‐613, thus leading to NPC metastasis. Conclusion: Our results highlight the importance of CYTOR in NPC development and provide new insights into potential therapeutic targets for NPC. [ABSTRACT FROM AUTHOR]

Associations between telomere length and cancer risk have been investigated in many epidemiological studies, but the results are controversial. These associations may be biased by reverse causation or confounded by environmental exposures. To avoid potential biases, we used Mendelian randomization method to evaluate whether TL is the causal risk factor for lung cancer. We conducted Mendelian randomization analysis in two published East Asian GWAS studies (7127 cases and 6818 controls). We used both weighted genetic risk score and inverse‐variance weighting method to estimate the relationship between TL and lung cancer risk. Nonlinear test also used to detect potential association trends. We observed that increased weight GRS was associated with increased risk of lung cancer (OR = 2.25, 95%CI: 1.81‐2.78, P = 1.18 × 10−13). In different subtypes, weight GRS was significantly associated with lung adenocarcinoma risk (OR = 2.69, 95% CI: 2.11‐3.42, P = 7.20 × 10−16); while lung squamous cell carcinoma showed a marginal association (OR = 1.45, 95% CI = 1.01‐2.10, P = .047). Nonlinear analysis suggested a log‐linear dose‐response relationship between increased weight GRS and lung cancer risk. Our results indicated that longer TL increases lung cancer risk. Those biological mechanisms changes caused by long TL may play an important role in lung carcinogenesis. [ABSTRACT FROM AUTHOR]

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: Although high‐risk human papillomavirus (HR‐HPV) infection is recognized as the main cause of cervical cancer, only a minority of HPV‐infected women develop this malignancy. Increasing evidence suggests that alterations of telomere length might be implicated in carcinogenesis. However, the association between cervical cancer and telomere length remains unknown. Methods: This case‐control study included 591 cervical cancer patients and 373 cancer‐free controls, all of whom were infected with HR‐HPV. Relative telomere length (RTL) in cervical cancer exfoliated cells was measured by quantitative PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis. Results: HPV16, 18, 52, and 58 were common in both case and control groups. The proportion of HPV16 infection tended to increase across the quartiles of RTL (Ptrend < 0.001). There was no statistically significant association of RTL with tumor differentiation, histological type, and FIGO stage. After adjustment for age and HPV types, the lowest quartile of RTL presented a 49% lower risk (OR = 0.51, 95% CI: 0.35, 0.76; P < 0.001) than those with the highest quartile of RTL. There was also a dose‐response relationship of shorter RTL on lower risk of cervical cancer (Ptrend < 0.001). Conclusion: Shortened telomere length in cervical exfoliated cells was related to the lower risk of cervical cancer among HR‐HPV‐positive women, which might help to improve cervical cancer screening and surveillance. Further prospective studies with large sample should be designed to validate our preliminary findings, and evaluate the potential efficacy of telomere length for cervical cancer screening. New triage biomarkers for human papillomavirus‐positive women are necessary to improve the identification of individuals at high risk of cervical cancer progression. Shorter telomere length in cervical exfoliated cells was associated with the lower risk of cervical cancer. Shortened telomere length may act as a protective factor in cervical carcinogenesis and represent a potential biomarker for this malignancy. [ABSTRACT FROM AUTHOR]

Cancer‐testis (CT) genes are a group of genes restrictedly expressed in testis and multiple cancers and can serve as candidate driver genes participating in the development of cancers. Our previous study identified a number of CT genes in nongerm cell tumors, but their expression pattern in testicular germ cell tumor (TGCT), a cancer type characterized by less genomic alterations, remained largely unknown. In this study, we systematically investigated the expression pattern of CT genes in TGCT samples and evaluated the transcriptome difference between TGCT and normal testis tissues, using datasets from the UCSC Xena platform, The Cancer Genome Atlas (TCGA) and the Genotype‐Tissue Expression (GTEx) project. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of expressed CT genes. We identified that 1036 testis‐specific expressed protein‐coding genes and 863 testis‐specific expressed long noncoding RNAs (lncRNAs) were expressed in TGCT samples, including 883 CT protein‐coding genes and 710 CT lncRNAs defined previously. The number of expressed CT genes was significantly higher in seminomas (P = 3.48 × 10−13) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS). In contrast, the number of expressed CT genes showed a moderate negative correlation with the fraction of copy number altered genomes (cor = −0.28, P = 1.20 × 10−3). Unlike other cancers, our analysis revealed that 96.16% of the CT genes were down‐regulated in TGCT samples, while CT genes in stem cell maintenance related pathways were up‐regulated. Further survival analysis provided evidence that CT genes could also predict the prognosis of TGCT patients with both disease‐free interval and progression‐free interval as clinical endpoints. Taken together, our study provided a global view of CT genes in TGCT and provided evidence that CT genes played important roles in the progression and maintenance of TGCT. [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]

Abstract: Emerging evidence indicates that circular RNAs (circRNAs) are implicated in cancer development. This study aimed to evaluate whether circulating circRNAs may serve as novel biomarkers for non‐small cell lung cancer (NSCLC). We used RNA sequencing (RNA‐seq) and quantitative real‐time PCR to explore cancer‐related circRNAs. Bioinformatics and functional analyses were performed to reveal biological effects of circRNAs on lung cancer cells. A total of 5471 distinct circRNAs were identified by total RNA‐seq, in which 185 were differentially expressed between cancerous and adjacent normal tissues. A circRNA derived from exon 5–7 of the FARSA gene, termed circFARSA, was observed to increase in cancerous tissues (P = 0.016), and was more abundant in patients’ plasma than controls (P < 0.001). Overexpression of circFARSA in A549 cell line significantly promoted cell migration and invasion. In silico analysis suggested that circFARSA might sponge miR‐330‐5p and miR‐326, thereby relieving their inhibitory effects on oncogene fatty acid synthase. Summarily, this study revealed circRNA profile of NSCLC for the first time and provided the evidence of plasma circFARSA as a potential noninvasive biomarker for this malignancy. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondria show the special role in cellular bioenergy and many essential physiological activities. Previous researches have suggested that variations of mitochondrial DNA copy number contribute to development of different types of carcinomas. However, the relationship of mtDNA copy number in peripheral blood leukocytes (PBLs) with the risk of head and neck squamous cell carcinoma (HNSCC) is still inconclusive. We investigated the association of mtDNA with HNSCC risk through a case–control study including 570 HNSCC cases and 597 cancer‐free controls. mtDNA copy number in PBLs was measured by real‐time qPCR. Logistic regression was performed to estimate the association between the mtDNA copy number in PBLs and HNSCC risk. A U‐shaped relation between the mtDNA copy number and HNSCC risk was found. Compared with those in the second quartile group, the adjusted odds ratios (ORs) and 95% confidence interval (CI) for those in the first and the forth quartile groups were 1.95 (1.37–2.76) and 2.16 (1.53–3.04), respectively. Using restricted cubic spline analysis, we confirmed such a significant U‐shaped relation. Furthermore, the U‐shaped association remained significant in different subgroups stratified by age, gender, tobacco smoking, and alcohol consumption. Both extremely low and high mtDNA copy numbers had significant associations with the increased HNSCC risk. [ABSTRACT FROM AUTHOR]

RAD51B plays a central role in homologous recombinational repair ( HRR) of DNA double-strand breaks ( DSBs), which is important to prevent genomic instability, a hallmark of cancer. Recent studies suggested that common genetic variants of RAD51B may contribute to cancer susceptibility. In this study, we aimed to investigate whether potentially functional variants within mi RNA-binding sites of RAD51B are associated with risk of cervical cancer. A total of 1486 cervical cancer patients and 1536 cancer-free controls were enrolled, and two genetic variants, rs963917 (A > G) and rs963918 (T > C), were genotyped in all participants. Using multivariate logistic regression analyses, we found that G allele of rs963917 conferred lower risk of cervical cancer compared to A allele (adjusted OR = 0.89, 95% CI = 0.80-0.99, P = 0.039). Similarly, rs963918 allele C was associated with a decreased risk for cervical cancer compared with allele T (adjusted OR = 0.84, 95% CI = 0.74-0.94, P = 0.004). Haplotype analyses showed that haplotype GC was also correlated with lower risk ( OR = 0.83, 95% CI = 0.73-0.95, P = 0.005) compared with the most common haplotype AT. In summary, our study suggested that mi RNA-binding site genetic variants of RAD51B may modify the susceptibility to cervical cancer, which is important to identify individuals with differential risk for this malignancy and to improve the effectiveness of preventive intervention. [ABSTRACT FROM AUTHOR]

Previously we identified that HBV(Hepatitis B virus) sequence variation, which may interact with host human leukocyte antigen ( HLA) genetic variation, could influence host risk of hepatocellular carcinoma ( HCC). More HBV-host interactions need to be identified. Protein tyrosine phosphatase nonreceptor type 12 ( PTPN12), serves as an antagonist to tyrosine kinase signaling, may play integral roles in immune response against HBV infection and the development of HCC. Rs11485985 was an expression quantitative trait loci ( eQTL) for PTPN12 by bioinformatics analyses. In this study, we genotyped the PTPN12 eQTL and sequenced the HBV region Enh II/ BCP/ PC in a case-control cohort including 1507 HBV-related HCC cases and 1560 HBV persistent carriers as controls. The variant genotype GG of rs11489585 increased HCC risk compared to the HBV persistent carriers (adjusted OR = 2.03, 95% confidence interval [ CIs] = 1.30-3.18). We also detected borderline significant associations of PTPN12 eQTL rs11489585 with HBV mutations ( P = 0.05 for G1799C). Taken together, PTPN12 may influence HCC risk accompanied by HBV mutations. [ABSTRACT FROM AUTHOR]

P21-activated kinase 1(PAK1) plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis and has been implicated with tumorigenesis and tumor progression. We hypothesized that functional polymorphisms in PAK1 gene may modify the risk of lung cancer. We screened four potentially functional polymorphisms (rs2154754, rs3015993, rs7109645, and rs2844337) in PAK1 gene and evaluated the association between the genetic variants and lung cancer risk in a case-control study including 1341 lung cancer cases and 1982 cancer-free controls in a Chinese population. We found that variant allele of rs2154754 was significantly associated with a decreased risk of lung cancer (OR = 0.85, 95% CI: 0.77-0.95, P = 0.004), meanwhile the result of rs3015993 was marginal (OR = 0.90, 95%CI: 0.81-1.00, P = 0.044). After multiple comparisons, rs2154754 was still significantly associated with the lung cancer risk (P < 0.0125 for Bonferroni correction). We also detected a significant interaction between rs2154754 genotypes and smoking levels on lung cancer risk (P = 0.042). Combined analysis of these two polymorphisms showed a significant allele-dosage association between the number of protective alleles and reduced risk of lung cancer (Ptrend = 0.008). These findings indicate that genetic variants in PAK1 gene may contribute to susceptibility to lung cancer in the Chinese population. [ABSTRACT FROM AUTHOR]