Silencing TTK expression inhibits the proliferation and progression of prostate cancer
EXPERIMENTAL CELL RESEARCH
Authors: Chen, Saipeng; Wang, Jianan; Wang, Lin; Peng, Huahong; Xiao, Longfei; Li, Changying; Lin, Dong; Yang, Kuo
Abstract
Purpose: The main objective of our study was to explore changes in the expression levels of differentially expressed genes associated with prostate cancer progression and to design a series of experiments to verify the function of differentially expressed genes. Method: The transcriptome datas of 499 cases of prostate cancer patients was downloaded from TCGA database. Differential genes associated with Gleason score were selected and filtered out by p < 0.05 and spearman coefficient > 0.3. KEGG signaling pathway was enriched by differentially expressed genes, and TTK was selected as the research object. The expression of TTK was tested in prostate cancer tissues and prostate cancer cell lines. The changes of biological behavior of prostate cancer cell lines were verified after UK was knocked out by siRNA and tumorigenic effect of TTK was verified by shRNA in vivo experiments. Result The expression of TTK was positively correlated with Gleason score of prostate cancer, and the expression of protein and mRNA in metastatic prostate cancer cell lines was higher than that in non-metastatic prostate cancer cell lines. Vitro biological experiments showed that TTK gene knockout could inhibit the proliferation, invasion and migration of PC3 and DU145 cells, and promote cell apoptosis. In vivo experiments showed that TTK knockout inhibited tumorigenesis in mice. It was found that the expression of CDK2 and CCNE1 decreased after TTK was knocked out. Conclusion: Our results suggest that TTK is a gene associated with malignancy of PCa and could be a novel therapeutic target for clinical application.
CCNE1 expression in high grade serous carcinoma does not correlate with chemoresistance
ONCOTARGET
Authors: Sapoznik, Stav; Aviel-Ronen, Sarit; Bahar-Shany, Keren; Zadok, Oranit; Levanon, Keren
Abstract
Delayed diagnosis of ovarian cancer, as well as high recurrence rates and lack of personalized therapy options, are among the causes for poor survival figures. Much effort is made towards developing new therapeutic possibilities, however predictive biomarkers are still unavailable. CCNE1 amplification, occurring in similar to 20% of the high grade serous ovarian tumors, was previously proposed as a marker for platinum resistance and poor prognosis as well as for CDK2 inhibition. The current study aimed to examine the role of CCNE1 positive-immunostain as a predictor of first-line taxane-platinum chemoresistance. We evaluated matched pre- vs. postneoadjuvant chemotherapy tumor samples and correlated the degree of pathological response to treatment with CCNE1 expression levels. Our results indicate that CCNE1 immunohistochemistry does not predict taxane-platinum chemoresistance in ovarian cancer patients. Further research is required in order to enable personalized adjuvant treatment, in cases where poor pathological response is achieved after the neoadjuvant phase.