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Objective:To investigate the expression of tripartite motif 14 (TRIM14) in human pancreatic cancer and analyze its relationship with clinicopathological features and prognosis, and further explore its functional mechanism in the development and progression of pancreatic cancer.Methods:176 pairs of pancreatic cancer tissues and corresponding adjacent tissues resected by surgery in Changhai Hospital affiliated with Navy Medical University from January 2016 to December 2018 were collected. The protein expression of TRIM14 in pancreatic cancer and adjacent normal tissue was detected by immunohistochemical staining. TRIM14 and phosphorylated p65 expression in pancreatic cancer was measured by western blotting. NF-κB targeting gene Bcl-xl, CCND1, VEGF-C mRNA was tested by real time quantitative PCR. The correlation between TRIM14 expression and clinicopathological characteristics was analyzed. The relationship between TRIM14 expression and tumor-free survival and overall survival of pancreatic cancer patients was evaluated by univariate and multivariate Cox regression model. The internal relationship between TRIM14 expression and the activation of NF-κB signaling pathway was analyzed.Results:The positive TRIM14 expression rate in pancreatic cancer was obviously higher than that in adjacent normal tissue [86.93%(153/176) vs 27.27%(48/176)], and the difference was statistically significant ( P<0.05). The expression level of TRIM14 was correlated with the clinical stage, lymph node metastasis and invasion depth of pancreatic cancer ( P=0.000, 0.000, 0.021), but not obviously with gender, age, differentiation degree and distant metastasis. Cox regression analysis showed that the expression level of TRIM14 was the independent risk factor for tumor-free survival ( RR=1.706, 95% CI 1.237-2.429, P=0.029) and overall survival ( RR=1.806, 95% CI 1.984-2.831, P=0.029). The expression level of TRIM14 was tightly associated with the phosphorylation level of p65 ( R=0.86, P<0.01), and the mRNA expression of Bcl-xl, CCND1 and VEGF-C was highly correlated with TRIM14 expression ( R=0.85-0.92, P<0.01). Conclusions:TRIM14 was highly expressed in pancreatic cancer tissues and was an independent risk factor for prognosis of pancreatic cancer patients. TRIM14 participates in the development and malignant progression of pancreatic cancer potentially via activating NF-κB pathway.
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Objective To detect miR-34a expression in pancreatic cancer tissue and BxPC3 cells,determine the target genes and analyze the correlation of the expression of miR-34a and its target genes with clinicopathological parameters in pancreatic cancer as well as the influence on the proliferation and migration abilities of BxPC3 cells.Methods c-MET 3'UTR dual-luciferase reporter vectors cloned wild-type and mutant c-MET 3'UTR to validate that c-MET was the target gene of miR-34a,respectively.Liposome was used to establish miR-34a overexpressing BxPC3 cells (miR-34a group) and c-MET downregulating BxPC3 cells (c-METsi group).qPCR,Western blot and IHC was used to measure the mRNA and protein expression of miR-34a and c-MET.The cell viability and migration ability of miR-34a overexpressing BxPC3 cells was assessed by CCK-8 and transwell assay.Results In miR-34a group,the 3'UTR of wild-type c-MET was obviously downregulated compared with that of control group [(65.00 ± 4.04) ％ vs 100％,P =0.00131)],but no statistical difference was found between two mutant groups,which proved that c MET was the target gene of miR-34a.The expression level of miR-34a was significantly down-regulated in cancer tissues compared to adjacent normal tissues by an average fold change of 1.92,and the difference was statistically significant (P =0.003).Compared with control group,c-MET mRNA and protein expression was obviously decreased in miR-34a group (0.045 ±0.003 vs 0.085 ±0.001,0.400±0.058 vs 1.133 ±0.120).After 4-day culture,the cell viability of miR-34a group and c-METsi group was obviously decreased (P =0.0012;P =0.0001),the transmembrane cells was also obviously decreased(231 ± 12 vs 351 ± 16,P =0.0039;259 ±7 vs 351 ± 16,P=0.0066),and the differences were statistically significant.miR-34a overexpression and c-MET positively expression in pancreatic cancer were significantly associated with TNM stage and tumor differentiation (P ＜0.001),and the expression of c-MET negatively correlated with miR-34a (P ＜0.001).Conclusions miR-34a was lowly expressed in pancreatic cancer,and its tumor suppressive activity may be partly through inhibiting c-MET.Overexpressing miR-34a or inhibiting c-MET may be new targets for the diagnosis and treatment of pancreatic cancer.
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Objective To study the expression of fascin, an actin bundling protein associated with cell motility, and the relationship with ER negative breast carcinoma.Methods Comparasion of the expression of fascin, estrogen receptor (ER) and proliferative cell nuclear antigen (PCNA) determined by immunohistological method was made on 84 specimens of primary breast carcinomas. Results The diffuse staining of fascin in cancerous cell cytoplasm was noted. Only 3 of 53 breast carcinomas with ER positive showed fascin positive expression (5.67%); in contrast, 21 of 31 carcinomas with ER-negative showed positive expression(67.7 %) (P