Hongwei Shen

High expression of CTHRC1 promotes EMT of epithelial ovarian cancer (EOC) and is associated with poor prognosis

Collagen triple helix repeat-containing 1 (CTHRC1) is aberrantly overexpressed in multiple malignant tumors. However, the expression characteristics and function of CTHRC1 in epithelial ovarian cancer (EOC) remain unclear. We found that CTHRC1 expression was up-regulated in the paraffin-embedded EOC tissues compared to borderline or benign tumor tissues. CTHRC1 expression was positively correlated with tumor size (p = 0.008), menopause (p = 0.037), clinical stage (p = 0.002) and lymph node metastasis (p < 0.001) and was also an important prognostic factor for the overall survival of EOC patients, as revealed by Kaplan-Meier analysis. CTHRC1 increased the invasive capabilities of EOC cells in vitro by activating the Wnt/β-catenin signaling pathway. We showed that ectopic transfection of CTHRC1 in EOC cells up-regulated the expression of EMT markers such as N-cadherin and vimentin, and EMT-associated transcriptional factor Snail. Knockdown of CTHRC1 expression in EOC cells resulted in down-regulation of N-cadherin, vimentin, Snail and translocation of β-catenin. Collectively, CTHRC1 may promote EOC metastasis through the induction of EMT process and serve as a potential biomarker for prognosis as well as a target for therapy.

Predictive Value of Excision Repair Cross-complementing Rodent Repair Deficiency Complementation Group 1 and Ovarian Cancer Risk

OBJECTIVE We aimed to analyze the association between excision repair cross-complementing rodent repair deficiency complementation group 1 (XRCC1) and ovarian cancer risk. METHODS We performed a hospital-based case-control study with 155 cases and 313 controls in China. All Chinese cases with newly diagnosed primary ovarian cancer between May 2005 to May 2010 in our hospital were invited to participate within 2 months of diagnosis. Controls were randomly selected from people who requested general health examinations in the same hospital during the same period. SNPs in EXCC1, ERCC1 C8092A and ERCC1 T19007C, were analyzed by PCR-RFLP method. RESULTS We observed a non-significantly increased risk of ovarian cancer among individuals with ERCC1 8092TT compared with those with the 8092CC genotype (adjusted OR=1.55, 95% CI%=0.74-2.97). Moreover, 19007TT genotype carriers also showed a non-significant increased risk of ovarian cancer over those with the 19007CC genotype (adjusted OR=1.78, 95% CI%=0.91-3.64). CONCLUSION Our firstly investigation of links between polymorphisms in the ERCC1 gene and the risk of ovarian cancer in Chinese population demonstrated no significant association. Further large sample studies in Chinese populations are needed.

Up-regulation of long non-coding RNA SNHG20 promotes ovarian cancer progression via Wnt/β-catenin signaling

Long non-coding RNA small nucleolar RNA host gene 20 (SNHG20) has been demonstrated to play crucial regulatory roles in many types of cancer. However, the biological function of long ncRNA (lncRNA) SNHG20 in ovarian cancer is still unclear. In the present study, we found that lncRNA SNHG20 was significantly increased in ovarian cancer. In addition, lncRNA SNHG20 knockdown suppressed the ovarian cancer progression, whereas overexpression of SNHG20 showed the opposite effects. Moreover, our results also revealed that lncRNA SNHG20 knockdown inhibited Wnt/β-catenin signaling activity by suppressing β-catenin expression and reversing the downstream target gene expression. Taken together, lncRNA SNHG20 plays an pivotal role in ovarian cancer progression by regulating Wnt/β-catenin signaling.

miR‑149‑5p promotes chemotherapeutic resistance in ovarian cancer via the inactivation of the Hippo signaling pathway

Chemotherapeutic resistance remains a critical clinical issue is responsible for treatment failure in patients with ovarian cancer. Evidence of the involvement of miRNAs in chemoresistance in ovarian cancer has been recently emerging. However, the underlying molecular links between chemoresistance and miRNAs remain largely unknown. In this study, we report that miR-149-5p expression is markedly elevated in chemoresistant ovarian cancer tissues compared with the chemosensitive ovarian cancer tissues. Furthermore, the silencing of miR-149-5p enhanced the chemosensitivity of ovarian cancer cells to cisplatin in vitro and in vivo. Conversely, the upregulation of miR-149-5p aggravated chemoresistance in ovarian cancer cells. Our results further revealed that miR-149-5p directly targeted the core kinase components of the Hippo signaling pathway, STE20-like kinase (MST)1 and protein salvador homolog 1 (SAV1), resulting in the inactivation of TEA domain (TEAD) transcription. On the whole, our findings reveal a novel mechanism of of action miR-149-5p in inducing chemotherapeutic resistance in ovarian cancer, indicating that miR-149-5p may serve as a chemotherapeutic response indicator and a potential therapeutic target in ovarian cancer.

Clinical significance of circulating tumor cells in predicting disease progression and chemotherapy resistance in patients with gestational choriocarcinoma: CTCs predict disease status in GC patients

Gestational choriocarcinoma (GC) is a highly aggressive tumor. In our study, we systematically investigated EpCAM/CD147 expression characteristics in patients with GC and assessed the role of circulating tumor cells (CTCs) in predicting chemotherapy response and disease progression. GC tissues were positive for either epithelial cellular adhesion molecule (EpCAM) or CD147, and all samples exhibited strong human chorionic gonadotropin (HCG) expression. Among all the recruited patients (n = 115), 103 had at least 1 CTC in a 7.5‐mL peripheral blood sample, and the percentage of patients with ≥4 CTCs in a particular FIGO stage group increased with a higher FIGO stage (p < 0.001). Furthermore, the pretreatment CTC count was related to tumor size (r = 0.225, p = 0.015) and the number of metastases (r = 0.603, p < 0.001). A progression analysis showed that among the 115 included patients who qualified for further examination, 52 of the 64 patients defined as progressive had ≥4 pretreatment CTCs, while only 7 of the 51 non‐progressive patients had ≥4 pretreatment CTCs (p < 0.001). In multivariate analysis, CTCs (≥4) remained the strongest predictor of PFS when other prognostic markers, FIGO score and FIGO stage were included. Moreover, based on the chemotherapy response, patients with ≥4 CTCs were more likely to be resistant to chemotherapy than those with <4 CTCs (P < 0.001). These findings demonstrates the feasibility of CTC detection in cases of GC by adopting EpCAM/CD147 antibodies together as capturing antibodies. The CTC count is a promising indicator in the evaluation of biological activities and the chemotherapy response in GC patients.

The oncogenic Golgi phosphoprotein 3 like overexpression is associated with cisplatin resistance in ovarian carcinoma and activating the NF-κB signaling pathway

BackgroundChemo-resistance is a leading cause of tumor relapse and treatment failure in patients with ovarian cancer. The identification of effective strategies to overcome drug resistance will have a significant clinical impact on the disease.MethodsThe protein and mRNA expression of GOLPH3L in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. 177 human ovarian cancer tissue samples were analyzed by IHC to investigate the association between GOLPH3L expression and the clinicopathological characteristics of ovarian cancer patients. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of GOLPH3L in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of GOLPH3L promotes chemoresistance in ovarian cancer cells.ResultsThe expression of GOLPH3L was markedly upregulated in ovarian cancer cell lines and tissues, and high GOLPH3L expression was associated with an aggressive phenotype and poor prognosis with ovarian cancer patients. GOLPH3L overexpression confers CDDP resistance on ovarian cancer cells; however, inhibition of GOLPH3L sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. Additionally, GOLPH3L upregulated the levels of nuclear p65 and phosphorylated inhibitor of nuclear factor Kappa-B kinase-β and IκBα, thereby activating canonical nuclear factor-κB (NF-κB) signaling.ConclusionsOur findings suggest that GOLPH3L is a potential therapeutic target for the treatment of ovarian cancer: targeting GOLPH3L signaling may represent a promising strategy to enhance platinum response in patients with chemoresistant ovarian cancer.