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Molecular Carcinogenesis

Iván Meneses-Morales, Eduardo Izquierdo-Torres, Lucía Flores-Peredo, Gabriela Rodríguez, Andrés Hernández-Oliveras, Angel Zarain-Herzberg
The knowledge about the role of calcium-regulated pathways in cancer cell growth and differentiation could be useful for the development of new therapeutic approaches to diminish its mortality. The ATP2A genes encode for SERCA pumps, which modulate cytosolic Ca2+ concentration, regulating various cellular processes including cell growth. ATP2A3 gene transcriptional down-regulation has been reported in gastric and colon cancer, but there is still a lack of understanding about the epigenetic processes regulating its transcription...
January 18, 2019: Molecular Carcinogenesis
Yuhui Tan, Xianli Wei, Yujuan Zhan, Kun Wang, Xiaolan Wang, Bonan Chen, Biaoyan Du, Jianyong Xiao
The protein EPHB4 plays a vital role in various tumor types. However, few studies into the function of circ-EPHB4 (hsa_circ_0001730) in tumors have been conducted. This study aimed to investigate the functions of circ-EPHB4 and the underlying mechanism of circ-EPHB4 in regulating hepatocellular carcinoma (HCC). The expression of circ-EPHB4 was found to be downregulated in HCC tumor tissues, whereas circ-EPHB4 overexpression suppressed cell viability, induced apoptosis, and inhibited cell migration and invasion in Huh7 and HepG2 cells...
January 15, 2019: Molecular Carcinogenesis
Ibrahim O Alanazi, Zafer Saad Al Shehri, Esmaeil Ebrahimie, Hassan Giahi, Manijeh Mohammadi-Dehcheshmeh
A considerable number of deposited variants has provided new possibilities for knowledge discovery in different types of prostate cancer. Here, we analysed variants located on 3'UTR, 5'UTR, CDs, Intergenic, and Intronic regions in castration-resistant prostate cancer (8496 variants), familial prostate cancer (3241 variants), metastatic castration-resistant prostate cancer (3693 variants), and prostate cancer (16599 variants). Chromosome regions 10p15-p14 and 2p13 were highly enriched (p < 0.00001) for variants located in 3'UTR, 5'UTR, CDs, intergenic, and intronic regions in castration-resistant prostate cancer...
January 15, 2019: Molecular Carcinogenesis
Safeena Kulsum, Nalini Raju, Nisheena Raghavan, Ravindra Dr, Anupam Sharma, Alka Mehta, Moni A Kuriakose, Amritha Suresh
Understanding the cellular interactions during oral carcinogenesis has the potential to identify novel prognostic and therapeutic targets. This study aimed at investigating the cancer stem cell (CSCs)-fibroblast niche interactions using in-vitro dysplastic cell line models developed from different stages of 4NQO-induced oral carcinogenic mice model. The spontaneously transformed epithelial cells (DysMSCTR6, 14 and 16) were developed from three time points (mild/moderate/severe), while 2 fibroblast cell lines (FibroMSCTR12, 16) were developed from moderate and severe dysplastic tissue...
January 15, 2019: Molecular Carcinogenesis
Hui Cheng, Chongmei Huang, Gusheng Tang, Huiying Qiu, Lei Gao, Weiping Zhang, Jianmin Wang, Jianmin Yang, Li Chen
Microsomal epoxide hyrolase 1 (EPHX1) is a critical biotransformation enzyme and participants in both the detoxification and activation of potentially genotoxic epoxides. In this study, we firstly aimed to investigate the role of EPHX1 in the chemoresistance of acute myeloid leukemic cells to aclarubicin (ACM) and mitoxantrone (MIT). EPHX1 mRNA expression and prognosis were measured in acute myeloid leukemia (AML) patients, and the function of EPHX1 in leukemic cell viability and apoptosis induced by ACM and MIT was also measured...
January 15, 2019: Molecular Carcinogenesis
Yan-Xia Zhou, Gabriela Fuentes-Creollo, Frank Ponce, Sasha A Langley, Kuang-Yu Jen, Susan E Celniker, Jian-Hua Mao, Antoine M Snijders
Variations in oral bacterial communities have been linked to oral cancer suggesting that the oral microbiome is an etiological factor that can influence oral cancer development. The 4-nitroquinoline 1-oxide (4-NQO)-induced murine oral and esophageal cancer model is frequently used to assess the effects of preventive and/or therapeutic agents. We used this model to assess the impact of the microbiome on tumorigenesis using axenic (germ-free) and conventionally housed mice. Increased toxicity was observed in germ-free mice, however, no difference in tumor incidence, multiplicity and size was observed...
January 10, 2019: Molecular Carcinogenesis
Xiaoxue Lv, Jiazhe Song, Kai Xue, Zhi Li, Ming Li, Danishi Zahid, Hongyu Cao, Lu Wang, Wanli Song, Tonghui Ma, Jianguo Gu, Wenzhe Li
Core fucosylation catalyzed by core fucosyltransferase (Fut8) contributes to the progressions of epithelial ovarian cancer (EOC). Copper transporter 1 (CTR1), which contains one N-glycan on Asn15 , mediates cellular transport of cisplatin (cDDP), and plays an important role in the process of cDDP-resistance in EOC. In the present study, we found that the core fucosylation level elevated significantly in the sera of cDDP-treated EOC patients. The in vitro assays also indicate that core fucosylation of CTR1 was significantly upregulated in cDDP-resistant A2780CP cells compared to the cDDP-sensitive A2780S cells...
January 5, 2019: Molecular Carcinogenesis
Beibei Zhu, Ying Zhu, Jianbo Tian, Na Shen, Jiaoyuan Li, Jiao Lou, Juntao Ke, Yang Yang, Yajie Gong, Jing Gong, Jiang Chang, Xiaoping Miao, Rong Zhong
9p21.3 has been identified as an unexpected hot point in multiple diseases GWAS including cancers, and we performed a two-stage case-control studies integrating functional assay strategy to find the potential functional variants modified susceptibility to pancreatic cancer (PC). An expanded Illumina HumanExome Beadchip of PC including 943 cases and 3908 controls was used to examine 39 tagSNPs in 9p21.3 and the promising single nucleotide polymorphism (SNP) was validated in stage 2 comprising 624 cases and 1048 controls...
January 3, 2019: Molecular Carcinogenesis
Xiupeng Zhang, Shuai Han, Haijing Zhou, Lin Cai, Jingduo Li, Nan Liu, Yang Liu, Liang Wang, Chuifeng Fan, Ailin Li, Yuan Miao
TIMM50 (Translocase of the inner mitochondrial membrane 50), also called TIM50, plays an essential role in mitochondrial membrane transportation. The existing literature suggests that TIMM50 may perform as an oncogenetic protein in breast cancer. However, the molecular mechanism, especially in human non-small cell lung cancer (NSCLC), is uncertain to date. In the present study, using immunohistochemistry, we found that TIMM50 expression significantly correlated with larger tumor size (P = 0.049), advanced TNM stage (P = 0...
January 3, 2019: Molecular Carcinogenesis
Jiawei Xu, Xiaohui Hua, Honglei Jin, Junlan Zhu, Yang Li, Jingxia Li, Chuangshu Huang
Although overexpression of the non-canonical NFκB subunit p52 has been observed in several tumors, the function and mechanism of p52 in bladder cancer (BC) are less well understood. Here, we aimed at understanding the role and mechanism underlying p52 regulation of BC invasion. Human p52 was stably knockdown with shRNA targeting p52 in two bladder cancer cell lines (T24 and UMUC3). Two constitutively expressing constructs, p52 and p100, were stably transfected in to T24 or UMUC3, respectively. The stable transfectants were used to determine function and mechanisms responsible for p52 regulation of BC invasion...
January 3, 2019: Molecular Carcinogenesis
Shiuh-Wen Luoh, Wendy Wagoner, Xiaoyan Wang, Zhi Hu, Xinhe Lai, Koei Chin, Rosalie Sears, Elizabeth Ramsey
GRB7 gene encodes a multi-domain signal transduction molecule and is part of the core of the HER-2 amplicon. GRB7 is commonly co-amplified and overexpressed with HER-2 in human breast cancer. This study addresses the role of GRB7 in HER-2 positive human breast cancers resistant to HER-2 targeted therapy. HCC1954, 21MT1 and JIMT1 are basal like HER-2 positive breast cancer cell lines based on expression profiling. These three cell lines are resistant to trastuzumab and lapatinib treatment. Knockdown of GRB7 protein expression with siRNA transfection as well as lentiviral vector mediated shRNA over-expression decreased the growth of HCC1954, 21MT1 and JIMT1 cells invitro and the growth of tumor xenograft these cells formed in animal models...
January 3, 2019: Molecular Carcinogenesis
Xiaodan Wang, Weiliang Zhong, Jingya Bu, Yuzhong Li, Ruihua Li, Rong Nie, Chenyang Xiao, Keli Ma, Xiaohua Huang, Ying Li
CD82, a member of the tetraspanin superfamily, has been proposed to exert its activity via tetra-transmembrane protein enriched microdomains (TEMs) in exosomes. The present study aimed to explore the potential of the exosome protein CD82 in diagnosing breast cancers of all stages and various histological subtypes in patients. The results strongly suggest that CD82 expression in breast cancer tissue was significantly lower than that in healthy and benign breast disease tissues. There was a significant negative correlation between CD82 expression in tissues and CD82 content in exosomes, which indicated that CD82 expression was redistributed from tissues to the blood with the development and metastasis of breast cancer...
January 3, 2019: Molecular Carcinogenesis
Xin Lu, Xiaohan Zhang, Yongjian Zhang, Kun Zhang, Chao Zhan, Xiuyun Shi, Yiqun Li, Jianxiang Zhao, Yunfan Bai, Yu Wang, Huan Nie, Yu Li
The carnitine shuttle system (CSS) plays a crucial role in the transportation of fatty acyls during fatty acid β-oxidation for energy supplementation, especially in cases of high energy demand, such as in cancer. In this study, to systematically characterize alterations of the CSS in hepatocellular carcinoma (HCC), acylcarnitine metabolic profiling was carried out on eighty pairs of HCC tissues and adjacent noncancerous tissues (ANTs) by using ultra-performance liquid chromatography coupled to mass spectrometry...
January 3, 2019: Molecular Carcinogenesis
Huaibiao Li, Shalmali Shukla, Lucien Frappart, Peter Herrlich, Aspasia Ploubidou
Loss-of-function of RHAMM causes hypofertility and testicular atrophy in young mice, followed by germ cell neoplasia in situ (GCNIS) of the testis, cellular atypia and development of the testicular germ cell tumour (TGCT) seminoma. These pathologies reflect the risk factors and phenotypes that precede seminoma development in humans and - given the high prevalence of RHAMM downregulation in human seminoma - link RHAMM dysfunction with the aetiology of male hypofertility and GCNIS-related TGCTs. The initiating event underlying these pathologies, in RHAMM mutant testis, is premature displacement of undifferentiated progenitors from the basal compartment...
December 23, 2018: Molecular Carcinogenesis
Valeria Bertagnolo, Silvia Grassilli, Stefano Volinia, Yasamin Al-Qassab, Federica Brugnoli, Federica Vezzali, Elisabetta Lambertini, Maria Palomba, Quirino Piubello, Enrico Orvieto, Cristina Natali, Maria Roberta Piva, Carlo Maria Croce, Silvano Capitani
Cells in non-invasive breast lesions are widely believed to possess molecular alterations that render them either susceptible or refractory to the acquisition of invasive capability. One such alteration could be the ectopic expression of the β2 isoform of phosphoinositide-dependent phospholipase C (PLC-β2), known to counteract the effects of hypoxia in low-invasive breast tumor-derived cells. Here, we studied the correlation between PLC-β2 levels and the propensity of non-invasive breast tumor cells to acquire malignant features...
December 23, 2018: Molecular Carcinogenesis
Giulia Lori, Paolo Paoli, Angelo Pietro Femia, Erica Pranzini, Anna Caselli, Katia Tortora, Andrea Romagnoli, Giovanni Raugei, Giovanna Caderni
LMW-PTP has been associated with the development of colorectal cancer (CRC) and with the resistance to chemotherapy in cancer cells. To clarify its role in vivo, we studied LMW-PTP expression in Pirc rats (F344/NTac-Apc am1137 ), genetically prone to CRC and resistant to apoptosis. In the morphologically normal mucosa (NM) of Pirc rats, a dramatic over-expression of LMW-PTP was found compared to wt rats (about 60 times higher). Moreover, LMW-PTP levels further increase in spontaneously developed Pirc colon tumors...
December 23, 2018: Molecular Carcinogenesis
Mingqing Wang, Wenbo Niu, Rong Hu, Yanjing Wang, Yangyang Liu, Lingyu Liu, Juan Zhong, Cha Zhang, Haiyan You, Jiaxing Zhang, Lu Lu, Lianbo Wei, Wei Xiao
RNA polymerase I subunit D (POLR1D), which is involved in synthesis of ribosomal RNA precursors and small RNAs, has been shown to be overexpressed in several human cancer types. Nevertheless, the role of POLR1D in the progression of colorectal cancer (CRC) remains unknown. The following study aimed to investigate the role and underlying mechanism of POLR1D in CRC progression. In this report, we found that POLR1D was significantly up-regulated in CRC through data mining of oncomine database. Furthermore, the immunohistochemistry (IHC) staining of a tissue microarray (TMA) of 75 human CRC patients showed that the expression level of POLR1D was positively correlated to tumor size and poor survival of CRC patients...
December 23, 2018: Molecular Carcinogenesis
Yalda Moayedi, Sophie A Greenberg, Blair A Jenkins, Kara L Marshall, Lina V Dimitrov, Aislyn M Nelson, David M Owens, Ellen A Lumpkin
Bioactive derivatives from the camphor laurel tree, Cinnamomum camphora, are posited to exhibit chemopreventive properties but the efficacy and mechanism of these natural products are not fully understood. We tested an essential-oil derivative, camphor white oil (CWO), for anti-tumor activity in a mouse model of keratinocyte-derived skin cancer. Daily topical treatment with CWO induced dramatic regression of pre-malignant skin tumors and a two-fold reduction in cutaneous squamous cell carcinomas. We next investigated underlying cellular and molecular mechanisms...
December 23, 2018: Molecular Carcinogenesis
Ariel L Hernandez, Ying Wang, Hilary L Somerset, Stephen B Keysar, Dara L Aisner, Carrie Marshall, Daniel W Bowles, Sana D Karam, David Raben, Antonio Jimeno, Marileila Varella-Garcia, Xiao-Jing Wang
Reports regarding the frequency of SMAD4 loss in human head and neck squamous cell carcinoma (HNSCC) vary significantly. We have shown that SMAD4 deletion contributes to HNSCC initiation and progression. Therefore, accurately detecting genetic SMAD4 loss is critical to determine prognosis and therapeutic interventions in personalized medicine. We developed a SMAD4 fluorescence in situ hybridization (FISH) assay to identify chromosomal SMAD4 loss at the single cell level of primary HNSCC specimens and patient derived xenograft (PDX) tumors derived from HNSCCs...
December 21, 2018: Molecular Carcinogenesis
Dae Wui Yoon, Yi-Sook Kim, Soyoung Hwang, Roza Khalmuratova, Mingyu Lee, Jee Hyun Kim, Gah Young Lee, Seong-Joon Koh, Jong-Wan Park, Hyun-Woo Shin
Intermittent hypoxia (IH), a characteristic of obstructive sleep apnea, is known to promote cancer progression and aggressiveness in mouse models. However, little is known regarding the effect of IH on cancer initiation. Here, the effect of IH on carcinogenesis was explored in azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon cancer models with 2 different protocols. In the first protocol, two other application time points (early or late initiation of IH) were applied. In the second protocol, mice were divided into only two groups, and then exposed to either N or IH conditions for 14 days...
December 21, 2018: Molecular Carcinogenesis
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