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Molecular Cancer

Maryam Moossavi, Negin Parsamanesh, Afsane Bahrami, Stephen L Atkin, Amirhossein Sahebkar
Inflammasomes are large intracellular multi-protein signalling complexes that are formed in the cytosolic compartment as an inflammatory immune response to endogenous danger signals. The formation of the inflammasome enables activation of an inflammatory protease caspase-1, pyroptosis initiation with the subsequent cleaving of the pro-inflammatory cytokines interleukin (IL)-1β and proIL-18 to produce active forms. The inflammasome complex consists of a Nod-like receptor (NLR), the adapter apoptosis-associated speck-like (ASC) protein, and Caspase-1...
November 17, 2018: Molecular Cancer
Dandan Li, Li Xiao, Yuetan Ge, Yu Fu, Wenqing Zhang, Hanwei Cao, Binbin Chen, Haibin Wang, Yan-Yan Zhan, Tianhui Hu
Tob1, a Tob/BTG anti-proliferative protein family member, functions as a tumour suppressor in many cancers. Here, we reveal a unique oncogenic role of Tob1 in colon cancer. Tob1 expression was upregulated during colon cancer progression, was significantly correlated with tumour size and tumour differentiation, and was a prognostic indicator of colon cancer. Unlike in other cancers, where nuclear Tob1 performs anticancer activity, Tob1 is predominantly localized in the cytosol of colon cancer cells, where this protein binds and stabilizes β-catenin to activate Wnt/β-catenin signalling, which in turn enhances Tob1 expression, thus forming a positive feedback loop to promote cell proliferation...
November 17, 2018: Molecular Cancer
Wei Zhai, Saiyang Li, Jin Zhang, Yonghui Chen, Junjie Ma, Wen Kong, Dongkui Gong, Junhua Zheng, Wei Xue, Yunfei Xu
PURPOSE: Although microRNAs (miRNAs) were revealed as crucial modulators in tumor metastasis and target therapy, our understanding of their roles in metastatic renal cell carcinoma (mRCC) and Sunitinib treatment was limited. Here we sought to identify human miRNAs that acted as key regulators in renal cancer metastasis and Sunitinib treatment. EXPERIMENTAL DESIGN: We focused on 2 published microarray data to select out our anchored miRNA and then explored the roles of miR-452-5p both in vitro and in vivo, which was downregulated after Sunitinib treatment while upregulated in metastasis renal cell carcinoma (RCC) tissues...
November 12, 2018: Molecular Cancer
Alex Root, Azadeh Beizaei, H Alexander Ebhardt
Developing combination therapy for castrate-resistant prostate cancer (CRPC) may require exploiting new drug targets outside androgen receptor and PI3K / AKT / mTOR signal transduction pathways implicated in prostate cancer (PCa) progression. One such possible new target is YWHAZ of the 14-3-3 protein family as this gene has prognostic significance for metastatic CRPC patients. However, there are no small molecules targeting YWHAZ commercially available. Hence, we explored whether the small molecule BV02 targeting another 14-3-3 protein family member SFN also binds to YWHAZ...
October 31, 2018: Molecular Cancer
Qi Wu, Si Sun, Zhiyu Li, Qian Yang, Bei Li, Shan Zhu, Lijun Wang, Juan Wu, Jingping Yuan, Changhua Yang, Juanjuan Li, Shengrong Sun
Emerging evidence supports the pivotal roles of cancer-associated cachexia in breast cancer progression. However, the mediators and mechanisms that mediate cancer-induced cachexia remain unclear. Here, we show that breast cancer-derived exosomes alter adipocytes and muscle cells in terms of increased catabolism characterized by the release of metabolites. Likewise, tumour cells cocultivated with mature adipocytes or C2C12 exhibit an aggressive phenotype through inducing epithelial-mesenchymal transition. Mechanistically, we show that cancer cell-secreted miR-155 promotes beige/brown differentiation and remodel metabolism in resident adipocytes by downregulating the PPARγ expression, but does not significantly affect biological conversion in C2C12...
October 25, 2018: Molecular Cancer
Shikha Saini, Kiara Tulla, Ajay V Maker, Kenneth D Burman, Bellur S Prabhakar
Thyroid cancer incidence is increasing at an alarming rate, almost tripling every decade. In 2017, it was the fifth most common cancer in women. Although the majority of thyroid tumors are curable, about 2-3% of thyroid cancers are refractory to standard treatments. These undifferentiated, highly aggressive and mostly chemo-resistant tumors are phenotypically-termed anaplastic thyroid cancer (ATC). ATCs are resistant to standard therapies and are extremely difficult to manage. In this review, we provide the information related to current and recently emerged first-line systemic therapy (Dabrafenib and Trametinib) along with promising therapeutics which are in clinical trials and may be incorporated into clinical practice in the future...
October 23, 2018: Molecular Cancer
Keqiang Zhang, Jinhui Wang, Lu Yang, Yate-Ching Yuan, Tommy R Tong, Jun Wu, Xinwei Yun, Melissa Bonner, Rajendra Pangeni, Zheng Liu, Tiger Yuchi, Jae Y Kim, Dan J Raz
BACKGROUND: Dysregulated histone methyltransferase G9a may represent a potential cancer therapeutic target. The roles of G9a in tumorigenesis and therapeutics are not well understood in non-small cell lung cancer (NSCLC). Here we investigated the impact of G9a on tumor growth and signaling pathways in NSCLC. METHODS: Immunohistochemistry analyzed G9a expression in NSCLC tissues. Both siRNA and selective inhibitor were used to target G9a. The impact of targeting G9a on key genes, signaling pathways and growth were investigated in NSCLC cells by RNA sequencing analysis, rescue experiments, and xenograft models...
October 22, 2018: Molecular Cancer
Maegan Miang Kee Lim, Jonathan Wei Kiat Wee, Jen Chi Soong, Damien Chua, Wei Ren Tan, Marco Lizwan, Yinliang Li, Ziqiang Teo, Wilson Wen Bin Goh, Pengcheng Zhu, Nguan Soon Tan
Overcoming multidrug resistance has always been a major challenge in cancer treatment. Recent evidence suggested epithelial-mesenchymal transition plays a role in MDR, but the mechanism behind this link remains unclear. We found that the expression of multiple ABC transporters was elevated in concordance with an increased drug efflux in cancer cells during EMT. The metastasis-related angiopoietin-like 4 (ANGPTL4) elevates cellular ATP to transcriptionally upregulate ABC transporters expression via the Myc and NF-κB signaling pathways...
October 20, 2018: Molecular Cancer
Hui Liu, Yuan Liu, Zhaolian Bian, Jing Zhang, Rui Zhang, Xiaoyu Chen, Yanxia Huang, Yang Wang, Jinshui Zhu
BACKGROUND: Circular RNAs (circRNAs) are a new type of non-coding RNAs and their functions in gastric cancer (GC) remain unclear. Recent studies have revealed that circRNAs play an important role in cancer development and certain types of pathological responses, acting as microRNA (miRNA) sponges to regulate gene expression. METHODS: CircNet was used to screen potential circRNAs and validated circYAP1 expression levels in 17 GC tissues by quantitative real-time PCR (qRT-PCR) and another 80 paired GC tissues by FISH...
October 18, 2018: Molecular Cancer
Hongyoon Choi, Kwon Joong Na
Although metabolic alterations are one of the hallmarks of cancer, there is a lack of understanding of how metabolic landscape is reconstituted according to cancer progression and which genetic alterations underlie its heterogeneity within cancer cells. Here, the configuration of the metabolic landscape according to genetic alteration is examined across 7648 subjects representing 29 cancers. The metabolic landscape and its reconfiguration according to the accumulated mutation maintained characteristics of their tissue of origin...
October 17, 2018: Molecular Cancer
Courtney M Schaal, Namrata Bora-Singhal, Durairaj Mohan Kumar, Srikumar P Chellappan
BACKGROUND: Lung cancer is the leading cause of cancer related deaths and its incidence is highly correlated with cigarette smoking. Nicotine, the addictive component of tobacco smoke, cannot initiate tumors, but can promote proliferation, migration, and invasion of cells in vitro and promote tumor growth and metastasis in vivo. This nicotine-mediated tumor promotion is facilitated through the activation of nicotinic acetylcholine receptors (nAChRs), specifically the α7 subunit. More recently, nicotine has been implicated in promoting self-renewal of stem-like side-population cells from lung cancers...
October 15, 2018: Molecular Cancer
Patrick Smeele, Sènan Mickaël d'Almeida, Clément Meiller, Anne-Laure Chéné, Charly Liddell, Laurent Cellerin, François Montagne, Sophie Deshayes, Sarah Benziane, Marie-Christine Copin, Paul Hofman, Françoise Le Pimpec-Barthes, Henri Porte, Arnaud Scherpereel, Marc Grégoire, Didier Jean, Christophe Blanquart
Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples...
October 11, 2018: Molecular Cancer
Zhenqiang Sun, Ke Shi, Shuaixi Yang, Jinbo Liu, Quanbo Zhou, Guixian Wang, Junmin Song, Zhen Li, Zhiyong Zhang, Weitang Yuan
Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance...
October 11, 2018: Molecular Cancer
Xu Zhang, Hui Shi, Xiao Yuan, Pengcheng Jiang, Hui Qian, Wenrong Xu
BACKGROUND: Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS: We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS: GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils...
October 6, 2018: Molecular Cancer
Giulia Cesi, Demetra Philippidou, Ines Kozar, Yeoun Jin Kim, Francois Bernardin, Guillaume Van Niel, Anke Wienecke-Baldacchino, Paul Felten, Elisabeth Letellier, Sonja Dengler, Dorothee Nashan, Claude Haan, Stephanie Kreis
BACKGROUND: Drug resistance remains an unsolved clinical issue in oncology. Despite promising initial responses obtained with BRAF and MEK kinase inhibitors, resistance to treatment develops within months in virtually all melanoma patients. METHODS: Microarray analyses were performed in BRAF inhibitor-sensitive and resistant cell lines to identify changes in the transcriptome that might play a role in resistance. siRNA approaches and kinase inhibitors were used to assess the involvement of the identified Anaplastic Lymphoma Kinase (ALK) in drug resistance...
October 5, 2018: Molecular Cancer
Fei Xie, Yawei Li, Miao Wang, Chao Huang, Dan Tao, Fuxin Zheng, Hui Zhang, Fuqing Zeng, Xingyuan Xiao, Guosong Jiang
BACKGROUND: Circular RNAs (circRNAs) are a new member of noncoding RNAs (ncRNAs) that have recently been described as key regulators of gene expression. Our previous study had identified the negative correlation between circHIPK3 and bladder cancer grade, invasion, as well as lymph node metastasis. However, the roles of circRNAs in cellular proliferation in bladder cancer remain largely unknown. METHODS: We had analyzed circRNA high-throughout sequencing from human tissues and determined bladder cancer related circRNA-3 (BCRC-3, GenBank: KU921434...
October 3, 2018: Molecular Cancer
Rui Zheng, Mulong Du, Xiaowei Wang, Weidong Xu, Jiayuan Liang, Wenying Wang, Qiang Lv, Chao Qin, Haiyan Chu, Meilin Wang, Lin Yuan, Jing Qian, Zhengdong Zhang
BACKGROUND: Extracellular communication within the tumor microenvironment plays a critical role in tumor progression. Although exosomes can package into long non-coding RNAs (lncRNAs) to mediate extracellular communication, the role of exosomal lncRNA PTENP1 in bladder cancer (BC) remains unclear. METHOD: We detected PTENP1 expression between patients with BC and healthy controls; the expression occurred in tissues and exosomes from plasma. We assessed the diagnostic accuracy by the receiver operating characteristic curve (ROC) and the area under curve (AUC)...
October 3, 2018: Molecular Cancer
Yao Zhan, Lutao Du, Lishui Wang, Xiumei Jiang, Shujun Zhang, Juan Li, Keqiang Yan, Weili Duan, Yinghui Zhao, Lili Wang, Yunshan Wang, Chuanxin Wang
Recently, expression signatures of exosomal long non-coding RNAs (lncRNAs) have been proposed as potential non-invasive biomarkers for cancer detection. In this study, we aimed to develop a urinary exosome (UE)-derived lncRNA panel for diagnosis and recurrence prediction of bladder cancer (BC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to screen and evaluate the expressions of eight candidate lncRNAs in a training set (208 urine samples) and a validation set (160 urine samples)...
September 29, 2018: Molecular Cancer
Mu Xu, Xiaoxiang Chen, Kang Lin, Kaixuan Zeng, Xiangxiang Liu, Bei Pan, Xueni Xu, Tao Xu, Xiuxiu Hu, Li Sun, Bangshun He, Yuqin Pan, Huiling Sun, Shukui Wang
BACKGROUND: Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles during the initiation and progression of cancers. In this study, we report that the small nucleolar RNA host gene 1 (SNHG1) is involved in colorectal cancer progression. METHODS: We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer. The effects of SNHG1 on colorectal cancer were investigated through in vitro and in vivo assays (i...
September 28, 2018: Molecular Cancer
Longqiang Wang, Xin Tong, Zhengyu Zhou, Shengjie Wang, Zhe Lei, Tianze Zhang, Zeyi Liu, Yuanyuan Zeng, Chang Li, Jun Zhao, Zhiyue Su, Cuijuan Zhang, Xia Liu, Guangquan Xu, Hong-Tao Zhang
BACKGROUND: TGF-β promotes tumor invasion and metastasis through inducing epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in human cancers. However, whether and how circRNAs contribute to TGF-β-induced EMT and metastasis in NSCLC remain vague. Here, we investigated the regulation and function of Circular RNA hsa_circ_0008305 (circPTK2) in TGF-β-induced EMT and tumor metastasis, as well as a link between circPTK2 and transcriptional intermediary factor 1 γ (TIF1γ) in NSCLC...
September 27, 2018: Molecular Cancer
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