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Wnt and Cervical Cancer

Hai Xu, Zhiyin Wang, Lang Xu, Guoyan Mo, Gangfeng Duan, Yali Wang, Zhengang Sun, Hao Chen
Chemotherapy has improved the clinical outcomes of cervical cancer patients. However, patients develop chemoresistance, whose underlying mechanisms are not well understood. In this study, we investigated the phosphorylation levels of eukaryotic translation initiation factor 4E (eIF4E) in cervical cancer cells subjected to chemotherapy. Results showed that chemotherapeutic drugs significantly increased eIF4E phosphorylation at S209 in HeLa and SiHa cells. Upregulation of phosphorylated eIF4E (p-eIF4E) levels has also been shown in cisplatin-resistant HeLa cells and has been observed to be a common response of cervical cancer patients undergoing chemotherapy...
2017: American Journal of Translational Research
Rong Zhang, Huan Lu, Yuan-Yuan Lyu, Xiao-Mei Yang, Lin-Yan Zhu, Guang-Dong Yang, Peng-Cheng Jiang, Yuan Re, Wei-Wei Song, Jin-Hao Wang, Can-Can Zhang, Fei Gu, Tian-Jiao Luo, Zhi-Yong Wu, Cong-Jian Xu
Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters...
March 17, 2017: Scientific Reports
Afsane Bahrami, Malihe Hasanzadeh, Soodabeh ShahidSales, Zohre Yousefi, Sima Kadkhodayan, Marjaneh Farazestanian, Mona Joudi Mashhad, Masoumeh Gharib, Seyed Mahdi Hassanian, Amir Avan
Cervical cancer is among the most commonly diagnosed cancer in women, supporting the need for identification of novel prognostic and predictive biomarkers to predict the risk of developing of this malignancy or predict the prognosis of patients. Against this background, the activation of the Wingless-type (Wnt)/β-catenin pathway has been suggested as the main dysregulated pathways, which is involved in the multistep process of cervical carcinogenesis, suggesting its value as a potential biomarker or therapeutic target...
March 16, 2017: Journal of Cellular Biochemistry
Fangmei Wang, Wenhuan Huang, Xiang Hu, Cheng Chen, Xinxin Li, Junlu Qiu, Zhongheng Liang, Jianmei Zhang, Limin Li, Xiaoqing Wang, Xiaofeng Ding, Shuanglin Xiang, Jian Zhang
Transcription factor AP-2β mediates the transcription of a number of genes implicated in mammalian development, cell proliferation and carcinogenesis. Although the expression pattern of AP-2β has been analyzed in cervical cancer cell lines, the functions and molecular mechanism of AP-2β are unknown. Here, we found that AP-2β significantly inhibits TCF/LEF reporter activity. Moreover, AP-2β and β-catenin interact both in vitro through GST pull-down assays and in vivo by co-immunoprecipitation. We further identified the interaction regions to the DNA-binding domain of AP-2β and the 1-9 Armadillo repeats of β-catenin...
March 9, 2017: Molecular Carcinogenesis
Pijun Gong, Yidong Wang, Yane Gao, Mei Gao, Lixia Liu, Ping Qu, Xinxing Jin, Qing Gao
Musashi1 (Msi1) is an RNA-binding protein that has been reported to be a pivotal regulator in tumorigenesis and progression in several cancers. However, its function and mechanism in cervical cancer is still unknown. In this study, Msi1 expression was found elevated in cervical cancers by immunohistochemistry and correlated with poor outcomes. Then, endogenous Msi1 was silenced in cervical cancer cell lines by short hairpin RNA (shRNA), and its function and mechanism were determined. The results showed that the silencing of Msi1 in SiHa and HeLa cells inhibited the cells' migratory and invasive abilities in vitro and tumor progression in vivo...
January 11, 2017: Human Pathology
Carolyn E Banister, Changlong Liu, Lucia Pirisi, Kim E Creek, Phillip J Buckhaults
BACKGROUND: Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 and E7 is thought to be necessary to maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, and most experimental therapies specifically target E6/E7. We investigated the presence and expression of HPV in cervical cancer, to correlate HPV oncogene expression with clinical and molecular features of these tumors that may be relevant to new targeted therapies...
February 21, 2017: Oncotarget
Jinxiao Liang, Hui Zhou, Yongpai Peng, Xiaofei Xie, Ruixin Li, Yunyun Liu, Qingsheng Xie, Zhongqiu Lin
Aberrant activation of the canonical Wnt pathway plays a significant role in cervical cancer (CC). However, limited data show the correlation between the cancer clinicopathological characteristics and the key molecules such as β-catenin and Wnt inhibitory factor 1 (WIF1). In this study, β-catenin and WIF1 expression were analyzed by immunohistochemistry for 196 patients with CC, 39 with cervical intraepithelial neoplasia (CIN), and 41 with normal cervical epithelium (NCE). Significant overexpression of β-catenin was detected in CC (67...
2016: BioMed Research International
Alireza Milani, Marzieh Basirnejad, Sepideh Shahbazi, Azam Bolhassani
Carotenoids and retinoids have several similarities in biological activities such as antioxidant properties, the inhibition of malignant tumor growth, and the induction of apoptosis. Supplementation with carotenoids can influence cell growth regulation, and modulate gene expression and immune response. Epidemiologic studies have shown the correlation of high carotenoid intake from food sources with reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular or eye diseases. Cancer chemoprevention by dietary carotenoids involves some approaches including gap junctional intercellular communication (GJIC), growth factor signaling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, Wnt/β-Catenin pathway, and inflammatory cytokines...
September 16, 2016: British Journal of Pharmacology
Annapurna Pranatharthi, Cecil Ross, Sweta Srivastava
Radiation is the most potent mode of cancer therapy; however, resistance to radiation therapy results in tumor relapse and subsequent fatality. The cancer stem cell (CSC), which has better DNA repair capability, has been shown to contribute to tumor resistance and is an important target for treatment. Signaling molecules such as Notch, Wnt, and DNA repair pathways regulate molecular mechanisms in CSCs; however, none of them have been translated into therapeutic targets. The RhoGTPases and their effector ROCK-signaling pathway, though important for tumor progression, have not been well studied in the context of radioresistance...
2016: Stem Cells International
Louise Bohr Mordhorst, Cecilia Ahlin, Bengt Sorbe
Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively...
September 27, 2016: Oncotarget
Ting Lu, Zhen Bao, Yunfeng Wang, Lixiang Yang, Bing Lu, Ke Yan, Shaozhen Wang, He Wei, Zhe Zhang, Gang Cui
Karyopherinβ1 (KPNB1), one of the cytosolic factors involved in the selective protein transport across nucleus, docked at nuclear pore complex and transported through nuclear envelope in an ATP-dependent style, assisting proteins to be recognized as import substrates. It has been reported to be bound up with the origination and progress of lung cancer, cervical cancer, head and neck cancer and hepatocellular carcinoma. In current study, we demonstrated for the first time that the role of KPNB1 in human glioma...
September 23, 2016: Biochemical and Biophysical Research Communications
Jun Liang, Lizhong Liang, Kexiong Ouyang, Zhiqiang Li, Xianping Yi
BACKGROUND: MALAT1 is recognized as an oncogenic lncRNA in various malignancies. However, its expression and function in oral tongue squamous cell carcinoma are still unknown. This study aims to investigate the expression and function of MALAT1 in TSCC tissues and cells. MATERIALS AND METHODS: qPCR was performed to detect the expression of MALAT1. MALAT1 was suppressed and upregulated by plasmid transfection in TSCC cells, and then cell migration, invasion, EMT, and apoptosis were analyzed...
February 2017: Journal of Oral Pathology & Medicine
Archita Ghoshal, Siddhartha Sankar Ghosh
The Wnt signaling pathway plays a predominant role in aberrant proliferation in myriad of cancers. In non-cancerous cells, Wnts are blocked by the secreted frizzled-related proteins (sFRPs) that are generally downregulated in cancer cells. We have purified and characterized bacterially expressed glutathione S-transferase-tagged SFRP4 from a novel clone generated from human cell origin. Cervical cancer (HeLa) and lung cancer (A549) cells, in which Wnt and associated genes were found to be expressed, were treated with the purified recombinant sFRP4, which revealed a significant dose-dependent cell growth inhibition up to 40 %...
July 2016: Molecular and Cellular Biochemistry
Maria Lee, Hee Jung Kim, Sang Wun Kim, Sun-Ae Park, Kyung-Hee Chun, Nam Hoon Cho, Yong Sang Song, Young Tae Kim
Evidence suggests that the long non-coding RNA (lncRNA), HOTAIR, is involved in cervical cancer pathogenesis. We examined serum HOTAIR expression levels in cervical cancer patients and determined the relationships between HOTAIR expression and several clinicopathological factors, including survival. We also examined the functional consequences of HOTAIR overexpression both in vitro and in vivo. Compared with control patients, HOTAIR expression was significantly greater in the serum of cervical cancer patients (P < 0...
July 12, 2016: Oncotarget
Xuan Wang, Ying Xia
microRNAs (miRNAs) play a vital role in tumor development and progression. In this study, we aimed to determine the expression and biological roles of miR-328 in cervical cancer and identify its direct target gene. Our data showed that miR-328 was significantly downregulated in human cervical cancer tissues and cells. Re-expression of miR-328 inhibited cervical cancer cell proliferation and colony formation in vitro and suppressed the growth of xenograft tumors in vivo. Bioinformatic analysis predicted TCF7L2 (an essential effector of canonical Wnt signaling) as a target gene of miR-328, which was confirmed by luciferase reporter assays...
June 24, 2016: Biochemical and Biophysical Research Communications
Qian Chen, Peng-Sheng Zheng, Wen-Ting Yang
Enhancer of zeste homolog 2 (EZH2), a catalytic core component of the Polycomb repressive complex 2 (PRC2), stimulates the silencing of target genes through histone H3 lysine 27 trimethylation (H3K27me3). Recent findings have indicated EZH2 is involved in the development and progression of various human cancers. However, the exact mechanism of EZH2 in the promotion of cervical cancer is largely unknown. Here, we show that EZH2 expression gradually increases during the progression of cervical cancer. We identified a significant positive correlation between EZH2 expression and cell proliferation in vitro and tumor formation in vivo by the up-regulation or down-regulation of EZH2 using CRISPR-Cas9-mediated gene editing technology and shRNA in HeLa and SiHa cells...
June 14, 2016: Oncotarget
Rui Xu, Jingye Hu, Tiansong Zhang, Chao Jiang, Hui-Yun Wang
Dysregulation of TRIM29 has been reported to be involved in tumorigenesis, but the role of TRIM29 in cervical cancer is unclear. In this study, we first examined TRIM29 expression and found that TRIM29 mRNA and protein expression was upregulated in cervical cancer tissues when compared with the matched adjacent cervical tissues. We further detected TRIM29 protein with immunohistochemistry in 150 paraffin-embedded samples from early-stage cervical cancer patients. The results showed that high expression of TRIM29 was significantly associated with pelvic lymph node metastasis (p=0...
May 10, 2016: Oncotarget
Zheng Li, Yang Yang, Yang Gao, Xiaoliu Wu, Xielan Yang, Yingjie Zhu, Hongying Yang, Lin Wu, Chengang Yang, Libing Song
Accumulating evidence has revealed that the expression of the lipid raft protein flotillin-1 is elevated in various human cancers, but the role flotillin-1 plays in the carcinogenesis of cervical cancer remains unclear. The expression profile of flotillin-1 was assayed using real-time PCR, western blotting, and immunohistochemical (IHC) staining in cervical cancer cell lines and cancer tissues with paired adjacent noncancerous cervical tissues. The expression of flotillin-1 protein was detected by IHC staining in a large cohort of 308 paraffin-embedded cervical cancer tissues...
2016: American Journal of Cancer Research
Nan Cui, Wen-Ting Yang, Peng-Sheng Zheng
Slug (Snai2) has been demonstrated to act as an oncogene or tumor suppressor in different human cancers, but the function of Slug in cervical cancer remains poorly understood. In this study, we demonstrated that Slug could suppress the proliferation of cervical cancer cells in vitro and tumor formation in vivo. Further experiments found that Slug could trans-suppress the expression of Akt1/p-Akt1 by binding to E-box motifs in the promoter of the Akt1 gene and then inhibit the cell proliferation and tumor formation of cervical cancer cells by up-regulating p21/p27 and/or down-regulating the activity of the Wnt/β-catenin signaling pathway...
May 3, 2016: Oncotarget
Heng Wei, Ning Wang, Yao Zhang, Shizhuo Wang, Xiaoao Pang, Shulan Zhang
Wnt-11 is a positive regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, Wnt-11 expression in cervical cancer has not been well investigated. The aim of this study was to investigate the role of Wnt-11 in cervical tumor proliferation and invasion. This study examined 24 normal cervical squamous epithelia, 29 cervical intraepithelial neoplasia (CIN), and 78 cervical cancer samples. The expression of Wnt-11 was investigated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction analysis...
September 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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