The effect and mechanism of miR-607/CANT1 axis in lung squamous carcinoma.

Lung squamous carcinoma (LUSC) is the second most frequent subtype of non-small cell lung cancer. Rarely gene alterations are identified in LUSC. Therefore, identifying LUSC-related genes to explain the relevant molecular mechanism is urgently needed. A potential biomarker, calcium-activated nucleotidase 1 (CANT1), was elevated in tissues of LUSC patients relative to normal cases based on the TCGA and/or GTEx database. CCK-8 and transwell tests were then implemented to measure the proliferative, invasive and migratory capacities, and showed that knockdown of CANT1 blocked LUSC cells proliferation. miR-607, predicted as an upstream factor for CANT1, was declined in LUSC using TargetScan analysis and luciferase activity test. Low miR-607 expression was related with unfavorable outcomes of LUSC patients. Moreover, miR-607 downregulation elevated cell viability, invasion and migration in LUSC cells, which was antagonized by si-CANT1. GEPIA website was accessed to estimate the relevance between CANT1 and epithelial-mesenchymal transition (EMT)-related positive factors. The protein levels of Fibronectin, Vimentin, Snail and ß-catenin were altered due to the abnormal CANT1 and miR-607 expression. Together, these data unveiled that miR-607/CANT1 pair may exert a vital role in the progression of LUSC through mediating EMT process, which would furnish an available therapeutic therapy for LUSC.

Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell-associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

Mutant p53 induces EZH2 expression and promotes epithelial-mesenchymal transition by disrupting p68-Drosha complex assembly and attenuating miR-26a processing.

The tumor suppressor p53 and the transcriptional repressor Enhancer of Zeste Homolog 2 (EZH2) have both been implicated in the regulation of epithelial-mesenchymal transition (EMT) and tumor metastasis via their impacts on microRNA expression. Here, we report that mutant p53 (mutp53) promotes EMT in endometrial carcinoma (EC) by disrupting p68-Drosha complex assembly. Overexpression of mutp53 has the opposite effect of wild-type p53 (WTp53), repressing miR-26a expression by reducing pri-miR-26a-1 processing in p53-null EC cells. Re-expression of miR-26a in mutp53 EC cells decreases cell invasion and promotes mesenchymal-epithelial transition (MET). Rescuing miR-26a expression also inhibits EZH2, N-cadherin, Vimentin, and Snail expression and induces E-cadherin expression both in vitro and in vivo. Moreover, patients with higher serum miR-26a levels have a better survival rate. These results suggest that p53 gain-of-function mutations accelerate EC tumor progression and metastasis by interfering with Drosha and p68 binding and pri-miR-26a-1 processing, resulting in reduced miR-26a expression and EZH2 overexpression.

[Use body fat determination instead of simple body composition parameters evaluate the risk of metabolic syndrome in Fuzhou adults].

OBJECTIVE: To compare the application of two different definitions of MS (IDF2005 and ATPIII2001) in this study population. According to IDF2005, evaluate the impact of body fat content and its distribution for the risk of metabolic syndrome. METHODS: The sample of 818 subjects measure the simple anthropometric parameters including body mass index (BMI), waist circumference, waist-hip ratio (WHR), and so on. Body fat mass and distribution were measured by dual-energy X-ray absorptiometry (DEXA). Quartile method is used to analyse the relevance ratio of MS in different value of BF and TF. ROC curve is used in evaluating of tipping point of BF, TF, simple body composition parameters and reliability of diagnosis. The risk of MS were analyzed by logistic regression. RESULTS: According to IDF2005, when BF, TF > or = P50. the relevance ratio of MS has a remarkable increasing (P < 0.01), its matching BMI is 24 and 23 kg/m2, according to NCEP ATPIII2001, when BF, TF > or =P75, the relevance ratio of MS has a remarkable increasing, too (P < 0.01), its matching BMI value is 26 kg/m2, BF and TF of MS patients which diagnosed by IDF2005 are lower than ATPIII2001 (P < 0.05). For each additional level of BF,the odds ratios of MS prevalence were 1.952 (male) and 2.644 (female); for each additional level of TF,the odds ratios of MS prevalence were 3. 276 (male) and 3.058 (female), BMI, WHR were not into the equation. The AUCROC which used to evaluate the exist of MS by BF and TF is larger than 0.9, and has better performance in sensitivity and specificity than BMI and WHR; the best point of contact of MS in BF is 25% (male), 35% (female), in TF is 30% (male), 38% (female). CONCLUSION: ATPIII standards may have been missed MS patients with normal high fasting blood glucose value and abdominal obesity. The application of IDF2005 standards was proved better in this population. Compared with simple anthropometric parameters, the accumulation of body fat, especially trunk fat even more harmful, to is better to identify the risk of MS in Fuzhou adults population.

[Application of real-time fluorescence quantitative PCR accompanied with comparison of Delta CT for diagnosis of Down's syndrome from a single cell].

OBJECTIVE: To evaluate the use of real-time fluorescence quantitative PCR (FQ-PCR) accompanied with comparison of Delta CT as a method for diagnosis of Down's syndrome from a single cell. METHODS: Single lymphocyte was isolated from the peripheral or umbilical cord blood samples of 22 clinically diagnosed Down's syndrome patients or fetus and 40 normal controls by micromanipulation techniques. Primer extension preamplification (PEP) and real-time FQ-PCR were used to amplify the S100B and DCSR1 located on chromosome 21, and GAPDH located on chromosome 12. Two pairs of DeltaCT values were compared between the two groups. The ratios of S100B/GAPDH and DSCR1/GAPDH products were calculated in trisomy 21 group. RESULTS: The DeltaCT values of Down's syndrome patients were significantly lower than those of normal controls. The difference between the two groups was statistically significant (P<0.01). The ratios of S100B/GAPDH and DSCR1/GAPDH products for trisomy 21 were 1.891(1.563-2.287) and 1.840 (1.562-2.168), respectively. CONCLUSION: Real-time FQ-PCR is a reliabe method that may provide a new way for non-invasive prenatal diagnosis and preimplantation genetic diagnosis for Down's syndrome.