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Background Epithelial–mesenchymal transition (EMT) and dysregulated microRNAs (miRNAs) have important roles in driving chemoresistance. We previously reported that iASPP is a key EMT inducer and could increase cisplatin resistance in cervical cancer (CC) cells. Herein, we investigate the downstream mechanisms through which iASPP contributes to EMT and cisplatin resistance in CC. Methods By using a lentiviral system, we investigated the effects of iASPP knockdown on CC cell growth and chemosensitivity of CC cells to cisplatin in vivo. We examined if miR-20a, which was up-regulated following iASPP overexpression, would influence metastatic phenotypes and cisplatin resistance in CC cells, and explored the possible molecular mechanisms involved. Results Knockdown of iASPP suppressed CC cell proliferation and sensitized CC cells to cisplatin in vivo. iASPP promotes miR-20a expression in a p53-dependent manner. Upregulation of miR-20a induced EMT and the recovery of CC cell invasion and cisplatin chemoresistance that was repressed by iASPP knockdown. We identified FBXL5 and BTG3 as two direct miR-20a targets. Silencing of FBXL5 and BTG3 restored cell invasion and cisplatin chemoresistance, which was suppressed by iASPP or miR-20a knockdown. Reduced FBXL5 and BTG3 expression was found in CC samples and associated with poor prognosis in CC patients. Conclusions iASPP promotes EMT and confers cisplatin resistance in CC via miR-20a-FBXL5/BTG3 signaling. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0520-6) contains supplementary material, which is available to authorized users.

Silencing of FBXL5 and BTG3 restored the effects that was suppressed by iASPP or miR-20a knockdown. (DOCX 1058Â kb)

Epithelial ovarian cancer (EOC) is one of the deadly gynecological malignancies. The function of protein kinase CK2α (CK2α) in EOC is still unknown. Our study aimed to investigate the relationship between the protein expression of CK2α and the tumor progression, the prognosis of human EOC. In this study, we analyzed the expression levels of CK2α through Western blot, using EOC cell lines like A2780, HO8910, COV644, OVCAR3, SKOV3, and the primary normal ovarian surface epithelial (NOSE) cells. Furthermore, OVCAR3 and SKOV3 EOC cells were employed as a cellular model to study the role of CK2α on cell growth, migration, invasion, apoptosis, and cell cycle distribution. In addition, we investigated CK2α protein expression in tumor tissues from patients with EOC by immunohistochemistry and analyzed the association between CK2α expression and clinicopathologic parameters and prognosis of EOC patients. And we found that compared with NOSE cells, CK2α protein expression was increased in A2780, HO8910, OVCAR3, and SKOV3 ovarian cancer cell lines. Decreased CK2α expression suppressed OVCAR3 and SKOV3 cell growth and induced more apoptosis. CK2α knockdown using specific siRNAs inhibited migration and invasion ability of OVCAR3 and SKOV3 cells. In addition, high CK2α protein expression was found in 68.4% (80/117) of EOC patients. Increased CK2α expression of was significantly correlated with FIGO staging and peritoneal cytology. Patients with higher CK2α expression had a significantly poorer overall survival compared with those with lower CK2α expression. Multi-variate Cox regression analysis proved that increased CK2α expression was an independent prognostic marker for EOC. Taken together, our data displayed that CK2α may play a role in tumor aggressive behavior of EOC and could be used as a marker for predicting prognosis of EOC patient. High CK2α expression might predict poor patient survival.

Pelvic lymphadenectomy has been widely performed as an essential part of the surgical treatment of early stage (IB-IIA) cervical cancer. In this study, the authors reviewed 128 patients who underwent this type of dissection to investigate the pattern of distribution and metastasis of deep obturator lymph node (DOLN) and parametrial lymph node (PLN), and the clinical hitstological factors that associated with detection of and metastasis to DOLN and PLN. The authors found the detection of DOLN and PLN significantly less common and more frequently unilateral compared with other groups of pelvic nodes. Tumor size and squamous cell carcinoma (SCC) antigen may help to identify patients suitable for individualized dissection of PLN.

Background Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. Methods SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. Results SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P

Background Protein tyrosine kinase 6 (PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis. However, PTK6 expression status and its role in cervical squamous cell cancer are unknown. This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen, early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues. The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed, paraffin-embedded, early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections. Results The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues. Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells. The level of PTK6 expression was significantly associated with tumor grade (P = 0.020). The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression (81.3% vs. 96.2%, P = 0.008). Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival (hazard ratio = 5.999, 95% confidence interval 1.622–22.191, P