The human ATF1 rs11169571 polymorphism associated with risk of nasopharyngeal carcinoma in Southern Chinese populations.

Our previous work reported activating transcription factor 1 (ATF1) is a promotive factor of nasopharyngeal carcinoma (NPC) tumorigenesis. This study is to further explore the association between the human ATF1 rs11169571 polymorphism and the risk of NPC occurrence. The association between ATF1 rs11169571 and risk of NPC occurrence was investigated in clinical samples of 560 patients and 661 controls obtained from southern China with high incidence of NPC. The genotypes were detected by PCR-RFLP. The differential expression activity of alleles -T and -C was analyzed with CNE-2 and C666-1 cells by luciferase reporter assay. Our data suggested that the allelic frequency and genotypes were significantly different between patients and controls. Compared to the TT homozygote, the TC and CC genotypes have been shown to be significantly decreased in NPC patients (OR = 0.494, 95% CI = 0.387-0.629, P < 0.001 and OR = 0.556, 95% CI = 0.364-0.851, P = 0.007, respectively). Compared to the -T allele, the -C allele is a factor of decreased risk in NPC (OR = 0.642, 95% CI = 0.537-0.767, P < 0.001). Luciferase reporter activity revealed that the -T allele confers a higher expression activity than the -C allele in CNE2 cells and C666-1 cells. In conclusion, ATF1 rs11169571 which could affect the expression of ATF1 is associated with NPC risk.

miR-221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-associated mortalities worldwide. MicroRNAs (miRNAs/miRs) serve important roles in tumor development, progression and metastasis. miR-221 has been reported to modulate proliferation, apoptosis, cell cycle distribution and cell migration in a variety of cancers. However, the function of miR-221 in the autophagy of cancer is unclear. In the present study, the role of miR-221 in the autophagy of CRC cells was investigated and its associated target was identified. Survival analysis using The Cancer Genome Atlas data suggested that a higher expression of miR-221 was associated with poor survival in patients with CRC. A Cell Counting kit-8 assay revealed that miR-221 promoted CRC cell proliferation. Autophagy flux analyzed by microtubule-associated protein 1 light chain 3 (LC3) turnover indicated that miR-221 reduced autophagy in CRC cells using different protease inhibitors (E64d and pepstatin A; Bafilomycin A1) in nutrient-rich medium or under starvation conditions. Tumor protein 53-induced nuclear protein 1 (TP53INP1) was identified as a potential novel target of miR-221 by bioinformative prediction. The protein expression of TP53INP1 was inversely regulated by miR-221 in CRC cells. Furthermore, luciferase activity assays were performed and indicated that miR-221 may regulate the luciferase activity of wild-type TP53INP1 without interfering with the activity of mutant TP53INP1. These data suggested that miR-221 may promote the cell proliferation of CRC via the inhibition of autophagy and targeted TP53INP1.

Association of microRNA-423 rs6505162 C>A polymorphism with susceptibility and metastasis of colorectal carcinoma.

Studies have evaluated the association between the SNP miRNA-423 rs6505162 C>A and cancer risk in several cancers with contradictory outcomes. It was reported that miRNA-423 rs6505162 C>A polymorphism was associated with the overall survival and the recurrence-free survival of colorectal carcinoma. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of colorectal carcinoma.In this study, we investigated the association between miRNA-423 polymorphism with risk and clinicopathological parameters of colorectal carcinoma. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype 117 colorectal carcinoma patients and 84 healthy controls.Our data indicated the frequencies of rs6505162 genotypes and alleles were significantly different between colorectal carcinoma patients and controls. Compared with CC homozygote, the AC heterozygote exhibited a significantly decreased risk of colorectal carcinoma; and the combination of AC and AA genotype was associated with decreased risk of colorectal carcinoma. The allele distribution of rs6505162 was significantly different between cases and controls. Furthermore, miR-423 rs6505162 C>A genotype showed a significant association with metastasis in patients (P = .022).Our study suggested that miR-423 rs6505162 C>A polymorphism was associated with the susceptibility and metastasis of colorectal carcinoma, and that miR-423 rs6505162 C>A polymorphism might be a potential biomarker for colorectal carcinoma.

Inhibitory effect of miR-451 on proliferation of hepatic carcinoma HepG2 cells and its prospect in hepatic carcinoma diagnosis and prognosis / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the mRNA molecular targets for diagnosis of hepatic carcionoma and to investigate their functional roles in proliferation and cell cycle of hepatic cancer cells. Methods: Based on the statistical analysis of miRNA expression data from 377 hepatic carcionoma samples and 37 adjacent non-cancerous samples in TCGAdatabase, a group of 33 differentially expressed miRNAs were identified.A further screen of these differentially expressed miRNAs was performed using the receiver operating characteristic curve (ROC curve) and Kaplan-Meier survival analysis; and with referring to the current publications, miR-451 was screened as the study subject. HepG2 cells were transfected with pLVX-shRNA2-miR-451 to over-express miR-451. The effect of miR-451 over-expression on the proliferation of HepG2 cell was determined by CCK-8 assay; while the effect on cell cycles was detected by flow cytometry. Results: The expression of miR-451 in the adjacent non-cancerous tissues was significantly lower than that in cancer tissues ([473.40±390.24] vs [1 990.47±2 118.04], P<0.05). MiR-451 could be used as an early diagnostic biomarker of hepatic carcionoma, with a high ROC value of 0.91 (sensitivity 0.89, specificity 0.87). The results of in vitro experiments showed that the proliferation of HepG2 cells was significantly decreased after miR-451 over-expression (48 h: [0.69±0.04] vs [1.08±0.05]; 72 h: [0.76±0.07] vs [1.52± 0.02]; all P<0.01), and a large number of cells were blocked in S phase(P<0.05). Conclusion: miR-451 has the potential to be used as a biomarker for hepatic carcionoma diagnosis and prognosis; moreover, it also exhibits the inhibitory effect on proliferation of hepatic cancer cells.

Functional PIN1 promoter polymorphisms associated with risk of nasopharyngeal carcinoma in Southern Chinese populations.

Our previous work reported the association between two single nucleotide polymorphisms (SNPs) in PIN1 promoter and nasopharyngeal carcinoma (NPC) risk with a small sample size in a low incidence area. This study investigated the association between the two SNPs and NPC risk in 733 patients and 895 controls from a high incidence area. The results indicated the genotype and allele frequencies of -842G > C and -667C > T were both significantly different between patients and controls even using the resampling statistics. The -842GC and -667TT genotypes showed a significantly increased risk of NPC (OR = 1.977, 95% CI = 1.339-2.919, P = 0.001 and OR = 1.438, 95% CI = 1.061-1.922, P = 0.019, respectively). Compared to the most common -842G-667C haplotype, -842G-667T haplotype and -842C-667C haplotype showed a significantly increased risk of NPC (OR = 1.215, 95% CI = 1.053-1.402, P = 0.008 and OR = 2.268, 95% CI = 1.530-3.362, P = 0.001, respectively). Further reporter gene expression suggested that variant -842C-667C and -842G-667T were associated with an enhanced transcriptional activity. In conclusion, our findings suggest that -842G > C and -667C > T in PIN1 promoter are associated with NPC risk; as well as the promoter activity is mediated by functional PIN1 variants.