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Molecular Carcinogenesis

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https://www.readbyqxmd.com/read/28418179/copy-number-variation-increased-gene-expression-and-molecular-mechanisms-of-neurofascin-in-lung-cancer
#1
Johanna Samulin Erdem, Yke Jildouw Arnoldussen, Vidar Skaug, Aage Haugen, Shanbeh Zienolddiny
Metastasis and cell adhesion are key aspects of cancer progression. Neurofascin (NFASC) is a member of the immunoglobulin superfamily of adhesion molecules and, while studies on NFASC are inadequate, other members have been indicated pivotal roles in cancer progression and metastasis. This study aimed at increasing the knowledge on the involvement of adhesion molecules in lung cancer progression by studying the regulation and role of NFASC in non-small cell lung cancer (NSCLC). Here, copy number variations in the NFASC gene were analyzed in tumor and non-tumorous lung tissues of 204 NSCLC patients...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418095/the-nuclear-orphan-receptor-nr4a1-regulates-%C3%AE-1-integrin-expression-in-pancreatic-and-colon-cancer-cells-and-can-be-targeted-by-nr4a1-antagonists
#2
Erik Hedrick, Syng-Ook Lee, Stephen Safe
β1-Integrin is highly expressed and is a negative prognostic factor for colon and pancreatic cancer patients and the gene plays a functional role in cell migration and invasion. In this study, we demonstrate that β1-integrin expression is regulated in pancreatic and colon cancer cells by the pro-oncogenic orphan nuclear receptor 4A1 (NR4A1, Nur77, TR3) and knockdown of this receptor by RNA interference decreases β1-integrin protein and mRNA expression, α5-integrin and also expression of β1-integrin-dependent phosphorylation of FAK (pFak)...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418088/rack1-forms-a-complex-with-fgfr1-and-pkm2-and-stimulates-the-growth-and-migration-of-squamous-lung-cancer-cells
#3
Chengzhi Zhou, Tao Chen, Zhanhong Xie, Yinyin Qin, Yangming Ou, Jiexia Zhang, Shiyue Li, Rongchang Chen, Nanshan Zhong
Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as well as cell growth in lung cancer. Better understanding the regulation of this process would benefit the clinical treatment for lung cancer. Here, it has been found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and inhibited the growth and migration of lung cancer cells, while over-expression of RACK1 in lung cancer cells led to the resistance to Erdafitinib...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418082/non-digestible-carbohydrates-supplementation-increases-mir-32-expression-in-the-healthy-human-colorectal-epithelium-a-randomized-controlled-trial
#4
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Bart Lagerwaard, Seamus Kelly, Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
Colorectal cancer (CRC) risk is modulated by diet and there is convincing evidence of reduced risk with higher non-digestible carbohydrates (NDCs) consumption. Resistant starch (RS), a NDC, positively modulates the expression of oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs protect against CRC. The present study aimed to investigate the effects of supplementation with two NDCs, RS and polydextrose (PD), on microRNA expression in the macroscopically-normal human rectal epithelium using samples from the DISC Study, a randomised, double-blind, placebo-controlled dietary intervention...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28418078/induction-of-mitochondrial-apoptotic-pathway-in-triple-negative-breast-carcinoma-cells-by-methylglyoxal-via-generation-of-reactive-oxygen-species
#5
Anirban Roy, Manisha Ahir, Saurav Bhattacharya, Pravat Kumar Parida, Arghya Adhikary, Kuladip Jana, Manju Ray
Triple negative breast cancer (TNBC) tends to form aggressive tumors associated with high mortality and morbidity which urge the need for development of new therapeutic strategies. Recently the normal metabolite Methylglyoxal (MG) has been documented for its anti-proliferative activity against human breast cancer. However, the mode of action of MG against triple negative breast cancer remains open to question. In our study, we investigated the anticancer activity of MG in MDA MB 231 and 4T1 TNBC cell lines and elucidated the underlying mechanisms...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398634/ski-regulates-smads-and-taz-signaling-to-suppress-lung-cancer-progression
#6
Mian Xie, Xiaojun Wu, Jinjun Zhang, Jiexia Zhang, Xiangxiang Li
Ski, the transforming protein of the avian Sloan-Kettering retrovirus, displays both pro-oncogenic and anti-oncogenic activities in human cancer. The mechanisms underlying these conflicting observations have not been fully understood. Herein, we investigated the mechanism underlying the tumor suppressor activity of Ski. To investigate the effect of Ski re-activation on TGF-β and Hippo/TAZ pathway, we measured its effect on the endogenous Smad target genes (PAI-1 and P15(INK4B) ) and TAZ target gene CTGF. The results revealed that Ski exerted its inhibitory activity in TGF-β1/Smad signaling pathway...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398627/aryl-hydrocarbon-receptor-promotes-hepatocellular-carcinoma-tumorigenesis-by-targeting-intestine-specific-homeobox-expression
#7
Shih-Hsien Hsu, Li-Ting Wang, Chee-Yin Chai, Chi-Cheng Wu, Edward Hsi, Shyh-Shin Chiou, Shen-Nien Wang
The aryl hydrocarbon receptor (AHR), a major chemical sensor, is thought to play a role in various biological contexts, including cell cycle regulation and tumorigenesis. However, its regulatory mechanisms remain unclear. We propose herein a novel mechanism through which AHR promotes tumorigenesis by targeting expression of the oncogene intestine-specific homeobox (ISX) in hepatocellular carcinoma (HCC). Compared to paired tumor-adjacent tissues and non-HCC tumors, HCCs exhibited an increased and hierarchical pattern of AHR expression...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398609/potentially-functional-variants-in-lncrnas-are-associated-with-breast-cancer-risk-in-a-chinese-population
#8
Yue Jiang, Fangzhi Du, Fei Chen, Na Qin, Zhu Jiang, Jing Zhou, Tao Jiang, Zhening Pu, Yue Cheng, Jiaping Chen, Juncheng Dai, Hongxia Ma, Guangfu Jin, Zhibin Hu, Hao Yu, Hongbing Shen
Long non-coding RNAs (lncRNAs) participate in the development of breast cancer. Genetic variants in lncRNAs may be involved in their abnormal expressions and associated with cancer risk. In the present study, we performed RNA sequencing on five paired breast cancer tumor and adjacent non-cancerous tissues to obtain differentially expressed lncRNAs. We systematically selected potential regulatory variants of these lncRNAs and investigated the associations between these variants and breast cancer susceptibility in 1,486 breast cancer cases and 1,519 cancer-free controls in a Chinese population...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28398603/kctd20-promotes-the-development-of-non-small-cell-lung-cancer-through-activating-fak-akt-pathway-and-predicts-poor-overall-survival-of-patients
#9
Xiupeng Zhang, Haijing Zhou, Lin Cai, Chuifeng Fan, Yang Liu, Liang Wang, Qingchang Li, Yuan Miao
Kctd20 (potassium channel tetramerization protein domain containing 20) is a positive regulator of Akt signaling. However, the role of Kctd20 during the course of tumorigenesis and development is unclear. Using immunohistochemistry, we demonstrated that, in non-small cell lung cancer (NSCLC) patients, Kctd20 protein expression significantly correlates with advanced TNM stage (P<0.001), positive status for regional lymph node metastasis (P=0.019) and poor overall survival (P=0.013). Proliferation and invasion assays showed that Kctd20 dramatically promotes the proliferation and invasion of NSCLC cells (P<0...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28383782/the-mir-200b-zeb1-circuit-regulates-diverse-stemness-of-human-hepatocellular-carcinoma
#10
Shu-Chun Tsai, Chen-Chun Lin, Tsung-Chieh Shih, Rong-Jeng Tseng, Ming-Chin Yu, Yu-Jr Lin, Sen-Yung Hsieh
Accumulating evidence suggests that human hepatocellular carcinoma (HCC) can be derived from cancer stem cells (CSCs), which contribute to tumor initiation, metastasis, chemoresistance, and recurrence. A great variety of HCC CSCs resulting in diverse clinical manifestations have been reported. However, how CSC diversity is regulated and generated remains unclear. Here we report that the miR-200b-ZEB1 circuit is closely involved with the induction and maintenance of a diverse group of CSCs. We found that miR-200b downregulation occurred in early HCC and associated with poor prognosis...
April 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28383763/upregulated-mir-132-in-lgr5-gastric-cancer-stem-cell-like-cells-contributes-to-cisplatin-resistance-via-sirt1-creb-abcg2-signaling-pathway
#11
Lanfang Zhang, Xiaohe Guo, Dezhong Zhang, Yingying Fan, Lei Qin, Shuping Dong, Lanfang Zhang
Cisplatin resistance has long been a major problem that restricts its use. A novel paradigm in tumor biology suggests that gastric tumor chemo-resistance is driven by gastric cancer stem cell-like (GCSCs). Growing evidence has indicated that microRNAs (miRNAs) contributes to chemo-resistance in gastric cancer (GC). Here, Lgr5(+) cells derived from gastric cancer cell lines displayed stem cell-like features. Flow cytometry demonstrated the presence of a variable fraction of Lgr5 in 19 out of 20 GC specimens...
April 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28370334/mir-27a-regulates-the-tgf-%C3%AE-signaling-pathway-by-targeting-smad2-and-smad4-in-lung-cancer
#12
Dong-Kyu Chae, Eunmi Ban, Young Sook Yoo, Eunice EunKyeong Kim, Ja-Hyun Baik, Eun Joo Song
The transforming growth factor-β (TGF-β) signaling pathway is associated with carcinogenesis and various biological processes. SMAD2 and SMAD4, which are putative tumor suppressors, have an important role in TGF-β signaling. The aberrant expression of these genes is implicated in some cancers. However, the mechanisms of SMAD2 and SMAD4 dysregulation are poorly understood. In this study, we observed that miR-27a was upregulated in lung cancer cell lines and patients. In addition, SMAD2 and SMAD4 genes were identified as targets of miR-27a by several target prediction databases and experimental validation...
March 31, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28370562/vitamin-c-at-high-concentrations-induces-cytotoxicity-in-malignant-melanoma-but-promotes-tumor-growth-at-low-concentrations
#13
Guang Yang, Yao Yan, Younan Ma, Yixin Yang
Vitamin C has been used in complementary and alternative medicine for cancers regardless of its ineffectiveness in clinical trials and the paradoxical effects antioxidants have on cancer. Vitamin C was found to induce cytotoxicity against cancers. However, the mechanisms of action have not been fully elucidated, and the effects of vitamin C on human malignant melanoma have not been examined. This study revealed that vitamin C at millimolar concentrations significantly reduced the cell viability as well as invasiveness, and induced apoptosis in human malignant melanoma cells...
March 30, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28345816/germline-variation-in-the-3-untranslated-region-of-the-pou2af1-gene-is-associated-with-susceptibility-to-lymphoma
#14
Kan Zhai, Jiang Chang, Jinlong Hu, Chen Wu, Dongxin Lin
Genetic variations in certain genes may alter the susceptibility to lymphoma. We searched electronic databases and selected candidate single-nucleotide polymorphisms (SNPs) located within 3'-untranslated regions (3'-UTRs) that might affect miRNA-binding ability in the 50 most dysregulated genes in lymphoma for further study. We found that rs1042752-located in the 3'-UTR of POU2AF1, which plays a vital role in lymphomagenesis-was significantly associated with lymphoma risk in a case-control study with 793 patients and 939 controls...
March 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28345808/molecular-genetic-analysis-of-the-melanoma-regulatory-locus-in-xiphophorus-interspecies-hybrids
#15
Yuan Lu, Mikki Boswell, William Boswell, Susanne Kneitz, Michael Hausmann, Barbara Klotz, Janine Regneri, Markita Savage, Angel Amores, John Postlethwait, Wesley Warren, Manfred Schartl, Ronald Walter
Development of spontaneous melanoma in Xiphophorus interspecies backcross hybrid progeny, (X. hellerii × [X. maculatus Jp 163 A × X. hellerii]) is due to Mendelian segregation of a oncogene (xmrk) and a molecularly uncharacterized locus, called R(Diff), on LG5. R(Diff) is thought to suppresses the activity of xmrk in healthy X. maculatus Jp 163 A parental species that rarely develop melanoma. To better understand the molecular genetics of R(Diff), we utilized RNA-Seq to study allele-specific gene expression of spontaneous melanoma tumors and corresponding normal skin samples derived from 15 first generation backcross (BC1 ) hybrids and 13 fifth generation (BC5 ) hybrids...
March 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28345805/promoter-hypermethylation-mediated-downregulation-of-mir-770-and-its-host-gene-meg3-a-long-non-coding-rna-in-the-development-of-gastric-cardia-adenocarcinoma
#16
Wei Guo, Zhiming Dong, Shengnan Liu, Yiling Qiao, Gang Kuang, Yanli Guo, Supeng Shen, Jia Liang
Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes an lncRNA and is downregulated in an expanding list of cancer cell lines and primary human cancers. The miR-770 is transcribed from the intronic sequence of MEG3 and MEG3 may be the host gene for miR-770. However, the biological role of MEG3 and miR-770 in gastric cardia adenocarcinoma (GCA) development and prognosis is poorly defined. The present study was to investigate the function and methylation status of MEG3 in GCA, and further to detect the functional association of miR-770 and its host gene MEG3 in GCA carcinogenesis and prognosis...
March 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28345785/nanog-overexpression-and-its-correlation-with-stem-cell-and-differentiation-markers-in-meningiomas-of-different-who-grades
#17
Diana Freitag, Aaron Lawson McLean, Michèle Simon, Arend Koch, Susanne Grube, Jan Walter, Rolf Kalff, Christian Ewald
NANOG, as a key regulator of pluripotency and acting synergistically with other factors, has been described as a crucial transcription factor in various types of cancer. In meningiomas the expression of this marker has not yet been described. With our study, we aimed to identify and localize NANOG and other possible markers of pluripotency, stem cell properties and differentiation in meningioma tissue, to elucidate a possible effect on tumorigenesis. The gene expression levels of NANOG (NANOG1 and NANOGP8), SOX2, OCT4, KLF4, ABCG2, CMYC, MSI1, CD44, NOTCH1, NES, SALL4B, TP53, and EPAS1 were quantitatively examined using RT-qPCR in 33 surgical specimens of low- (WHO grade I) as well as in high-grade (WHO grade II/III) meningiomas with dural tissue as reference...
March 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277622/abortifacient-metapristone-ru486-derivative-interrupts-cxcl12-cxcr4-axis-for-ovarian-metastatic-chemoprevention
#18
Ning Zheng, Jiahang Chen, Tao Li, Weiqun Liu, Jian Liu, Hongning Chen, Jichuang Wang, Lee Jia
Recent global epidemiological studies revealed the lower ovarian cancer death from long-term use of oral contraceptives. However, the underlying mechanism of action is not clear. Here, we use the abortifacient metapristone (RU486 derivative) to test the hypothesis that the contraceptives might interrupt CXCL12/CXCR4 chemokine axis to inhibit ovarian cancer metastasis. Metapristone at concentrations (<IC50) remarkably reduces CXCL12-induced CXCR4 expression on ovarian SKOV-3 and IGROV-1 cell lines, and down-regulates the CXCR4-related mRNAs and intracellular proteins...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277619/loss-of-desmoglein-2-promotes-tumorigenic-behavior-in-pancreatic-cancer-cells
#19
Katharina Hütz, Julian Zeiler, Lena Sachs, Steffen Ormanns, Volker Spindler
The ability to maintain cell-cell adhesion is crucial for tissue integrity and organization. Accordingly, loss of cohesiveness plays a critical role in cancer invasion and metastasis. Desmosomes are cell junctions providing strong intercellular adhesive strength and dysregulation of desmosomal constituents contributes to cancer progression through altered cell signaling pathways. Here, we focused on the desmosomal adhesion molecules Desmoglein 2 (Dsg2) and Desmocollin 2 (Dsc2), and their contribution to migration and invasion in pancreatic cancer cells...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28277616/-e-2-methoxy-4-3-4-methoxyphenyl-prop-1-en-1-yl-phenol-suppresses-ovarian-cancer-cell-growth-via-inhibition-of-erk-and-stat3
#20
Jie Zheng, Dong Ju Son, Hye Lim Lee, Hee Pom Lee, Tae Hoon Kim, Jung Heun Joo, Young Wan Ham, Wun Jae Kim, Jae Kyung Jung, Sang-Bae Han, Jin Tae Hong
In the present study, we synthesized several non-aldehyde analogues of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal which showed anti-cancer effect. Interestingly, among the 16 compounds, we found that (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP) showed the most significant anti-proliferative effect on PA-1 and SK-OV-3 ovarian epithelial cancer cells. MMPP treatment (0-15 µg/mL) induced apoptotic cell death, enhanced the expression of cleaved caspase-3, and cleaved caspase-9 in a concentration dependent manner...
March 9, 2017: Molecular Carcinogenesis
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