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.

A novel microRNAs expression signature for hepatocellular carcinoma diagnosis and prognosis.

This study aims to identify prognostic microRNAs (miRNAs) biomarkers for diagnosis and survival of hepatocellular carcinoma (HCC) based on large patients cohort analysis. HCC patient cohort data were downloaded from The Cancer Genome Atlas, including paired HCC and adjacent non-cancer tissues. Receiver operating characteristic curve method was used to classify cancer and non-cancer tissues according to microRNAs expression levels. The aberrant microRNAs expression level were ranked and risked for building a prognostic miRNAs signature model. Kaplan-Meier survival was used to analyze the differences among various risk factors in accordance with miRNAs ranking scores. The study showed 33-miRNA signature, 11 were down-regulated and 22 were up-regulated through comparison between cancer samples and non-cancer samples. The maximum correct classification rate is up to 98.7%. Five microRNAs, hsa-mir-3677, hsa-mir-421, hsa-mir-326, hsa-mir-424 and hsa-mir-511-2, significantly correlated with patient survival. The survival rate and time negatively associated with lowering miRNAs index. In the low risk group, over 70% patients showed 5 years survival, while none patients survived longer than 5 years in the high risk group. MiR-424, miR-326 and miR-511 could be applied for HCC diagnostic biomarkers. These five miRNAs were significantly associated with lysosome pathway and D-Glutamine and D-glutamate metabolism pathway via Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology annotation. Conclusively, the five miRNAs expression signature could be used as HCC prognostic and diagnostic biomarkers.