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Molecular Carcinogenesis

Ruizhi Wang, Yi Jin, Xue-Hua Yao, Wenzhe Fan, Jiang Zhang, Yihai Cao, Jiaping Li
Hepatocellular carcinoma (HCC) manifests as a highly metastatic cancer with extremely poor prognosis. However, mechanisms underlying metastasis of HCC are not fully understood. Here, we showed that switching gene expression from MAT1A to MAT2A (M1-M2 switch) promoted cancer invasion and metastasis. Reversion of the M1-M2 switch repressed, whereas enhancing the M1-M2 switch promoted the ability of HCC cells to metastasize. Moreover, we provided clinical data showing that tipping the balance between MAT1A and MAT2A expression correlated with increased metastasis and inferior recurrence-free survival in HCC patients...
May 10, 2018: Molecular Carcinogenesis
Huan Yang, Hailong Fu, Bo Wang, Xu Zhang, Jiahui Mao, Xia Li, Mei Wang, Zixuan Sun, Hui Qian, Wenrong Xu
Exosomes are critically involved in tumor growth, metastasis, and therapy resistance. Exosomes have the potential to be utilized as cancer biomarkers. In this study, we aimed to explore the roles and clinical values of exosomal miRNAs in gastric cancer. We found that the concentration of exosomes was significantly higher in the serum of gastric cancer patients and the culture supernatants of gastric cancer cells than that in healthy volunteers and gastric mucosa epithelial cells. In particular, miR-423-5p was elevated in the serum exosomes of gastric cancer patients, and the level of exosomal miR-423-5p was remarkably correlated with lymph node metastasis...
May 10, 2018: Molecular Carcinogenesis
Yanqing Zhou, Zhanyao Tan, Kun Chen, Wenjiao Wu, Jinrong Zhu, Geyan Wu, Lixue Cao, Xin Zhang, Xin Zeng, Jun Li, Wei Zhang
Gliomas are common, aggressive central nervous system tumors with poor overall survival rates. Despite improvements in neurosurgery, chemotherapy and radiotherapy, the outcomes of patients with malignant gliomas remain poor. Therefore, increased knowledge of the molecular mechanisms that regulate glioma progression is crucial to identify novel therapeutic targets. Here, we reported that SHCBP1, a member of Src homolog and collagen homolog (Shc) family, was significantly overexpressed in glioma tissues and glioma cell lines compared to the corresponding normal tissues and cells...
May 10, 2018: Molecular Carcinogenesis
Y P Du, L L Wang, S Chen, Y Liu, Y Zhao
lncRNA DLEU1 as a non-coding gene, involves in the occurrence and development of multiple tumors. However, there is no related report in endometrial carcinoma. In order to focus on the role and mechanism of lncRNA DLEU1 in endometrial carcinoma, we used qRT-PCR to detect the expression of lncRNA DLEU1 and found that lncRNA DLEU1 was highly expressed in endometrial carcinoma. Moreover, compared to Ishikawa and KLE, lncRNA DLEU1 was higher in HEC-1B. In addition, Up-regulation of lncRNA DLEU1 promoted cell viability, migration, invasion and reduced the proportion of apoptosis...
May 10, 2018: Molecular Carcinogenesis
Deepanshi Dhar, Gagan Deep, Sushil Kumar, Michael F Wempe, Komal Raina, Chapla Agarwal, Rajesh Agarwal
Pancreatic cancer (PanC) is one of the deadliest malignancies worldwide and frontline treatment with gemcitabine becomes eventually ineffective due to increasing PanC resistance, suggesting additional approaches are needed to manage PanC. Recently, we have shown the efficacy of bitter melon juice (BMJ) against PanC cells, including those resistant to gemcitabine. Since cancer stem cells (CSCs) are actively involved in PanC initiation, progression, relapse and drug-resistance, here we assessed BMJ ability in targeting pancreatic cancer-associated cancer stem cells (PanC-CSCs)...
May 4, 2018: Molecular Carcinogenesis
Rishi Kumar Jaiswal, Pramod Kumar, Manoj Kumar, Pramod Kumar Yadava
Telomerase complex maintains the length of the telomere and protects erosion of the physical ends of the eukaryotic chromosome in all actively dividing cells including cancer cells. Telomerase activation extends the lifespan of cells in culture by maintaining the length of the telomere. Compared to terminally differentiated somatic cells, telomerase activity remains high in over 90% of cancer cells. It has now become clear that the role of telomerase is much more complex than just telomere lengthening. The remaining 10% of cancers deploy ALT (alternative lengthening of telomeres) pathway to maintain telomere length...
May 2, 2018: Molecular Carcinogenesis
Jian Chen, Xing Zhang, Yong Wang, Yu Ye, Zhaoquan Huang
For postmenopausal cardiovascular disease, long-term estrogen therapy may increase the risk of breast cancer. To reduce this risk, estrogen may be replaced with the phytoestrogen formononetin, but how formononetin acts on vascular endothelial cells (ECs) and breast cancer cells is unclear. Here, we show that low concentrations of formononetin induced proliferation and inhibited apoptosis more strongly in cultured human umbilical vein endothelial cells (HUVECs) than in breast cancer cells expressing estrogen receptor α (ERα) (MCF-7, BT474) or not (MDA-MB-231), and that this differential stimulation was associated with miR-375 up-regulation in HUVECs...
May 2, 2018: Molecular Carcinogenesis
Qin Zheng, Chen Wang, Liang Wang, Di Zhang, Nan Liu, Xiaocui Ming, Haitao Zhou, Qiere Guli, Yang Liu
Basic helix-loop-helix family member e40 (BHLHE40) is located in 3p26.1 and acts as a transcriptional repressor of the circadian rhythm by suppressing the expression of the clock genes and clock-controlled genes. Recent research indicated that BHLHE40 may be involved in regulating tumor cell progression. However the mechanism by which BHLHE40 regulates the invasion and metastasis of tumor cells is unclear. Our in vitro assays showed that BHLHE40 promoted tumor cell invasion while BHLHE40 silencing by siRNA suppressed tumor cell invasion of MCF-7 cells...
April 28, 2018: Molecular Carcinogenesis
Mandakini J Patel, Shreya Tripathy, Keya D Mukhopadhyay, Tamna Wangjam, April B Cabang, Jay Morris, Michael J Wargovich
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death in men and women in the United States. Anti-inflammatory blockade has been proven to be a promising avenue of colorectal cancer prevention. However, NSAIDs while effective in curbing CRC risk are too toxic for long-term use in cancer prevention. The Neem tree (Azadirachta indica) is rich in liminoid terpenoids, collectively known as azadiractoids and has been shown to have anti-inflammatory effects...
April 26, 2018: Molecular Carcinogenesis
Jinglin Zhang, Yuhang Zhou, Tingting Huang, Feng Wu, Liping Liu, Johnny S H Kwan, Alfred S L Cheng, Jun Yu, Ka Fai To, Wei Kang
Gastric cancer (GC) is one of the most common malignancies in Asian areas. PIEZO1 has been implied to regulate epithelial homeostasis to play an important role in physiological processes. It is also related to tumor initiation and progression. However, the role of PIEZO1 has not yet been explored in GC. The expression of PIEZO1 in GC cell lines and primary samples was determined by qRT-PCR and Western blot. The clinical correlation of PIEZO1 in GC was evaluated by immunohistochemistry on tissue microarray. The oncogenic role of PIEZO1 was demonstrated in gastric tumorigenesis through a series of functional assays, including cell proliferation, cell invasion and flow cytometry analysis...
April 23, 2018: Molecular Carcinogenesis
Naveen A Mallangada, Joselin M Vargas, Swaroopa Thomas, Matthew G DiGiovanni, Brandon M Vaeth, Matthew D Nemesure, Ruixue Wang, Joseph F LaComb, Jennie L Williams, Lorne M Golub, Francis Johnson, Gerardo G Mackenzie
Pancreatic Cancer (PC) is a deadly disease in need of new therapeutic options. We recently developed a novel tricarbonylmethane agent (CMC2.24) as a therapeutic agent for PC, and evaluated its efficacy in preclinical models of PC. CMC2.24 inhibited the growth of various human PC cell lines in a concentration and time-dependent manner. Normal human pancreatic epithelial cells were resistant to CMC2.24, indicating selectivity. CMC2.24 reduced the growth of subcutaneous and orthotopic PC xenografts in mice by up to 65% (p < 0...
April 23, 2018: Molecular Carcinogenesis
Archana Katoch, Sujit Suklabaidya, Souneek Chakraborty, Debasis Nayak, Reyaz Ur Rasool, Deepak Sharma, Debaraj Mukherjee, Mir Mohd Faheem, Anmol Kumar, Parduman Raj Sharma, Shantibhusan Senapati, Lekha Dinesh Kumar, Anindya Goswami
Epithelial-mesenchymal transition (EMT), a critical event that occurs during invasion and metastatic spread of cancer cells. Here, we conceive a dual mechanism of Par-4-mediated inhibition of EMT and induction of MET in metastatic pancreatic cancer cells. First, we demonstrate that 1,1'-β-D-glucopyranosyl-3,3'-bis(5-bromoindolyl)-octyl methane (NGD16), an N-glycosylated derivative of medicinally important phytochemical 3,3'-diindolylmethane (DIM) abrogates EMT by inducing pro-apoptotic protein Par-4. Induction of Par-4 (by NGD16 or ectopic overexpression) strongly impedes invasion with inhibition of major mesenchymal markers viz...
April 19, 2018: Molecular Carcinogenesis
Ya-Hui Huang, Kwang-Huei Lin, Jao-Song Yu, Ting-Jung Wu, Wei-Chen Lee, Chuck C-K Chao, Tai-Long Pan, Chau-Ting Yeh
Heat shock protein 60 (HSP60) overexpresses in various types of cancer, but its expression levels and functions in hepatocellular carcinoma (HCC) are still in dispute. We aim to clarify this issue and examine whether HSP60 could be a therapeutic target for HCC. We found drastically enhanced cell apoptosis and suppressed cell proliferation in two HCC cell lines with HSP60-silencing, and also indicated survivin is involved in this regulatory process in vitro and in vivo. However, HSP60-silencing in normal human hepatocytes only resulted in a minimal reduction of cell proliferation but without effects on cell apoptosis...
April 19, 2018: Molecular Carcinogenesis
Wei Wu, Deepkamal Karelia, Kartick Pramanik, Shantu G Amin, Arun K Sharma, Cheng Jiang, Junxuan Lu
Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNCaP prostate cancer cells with ISC-4 and examined their apoptosis responses, and interrogated the signaling mechanisms through pharmacological and siRNA knockdown approaches. Our results show that ISC-4 was more potent at inducing apoptosis than its sulfur analog phenylbutyl isothiocyanate (PBITC) without suppressing protein kinase AKT Ser473 phosphorylation...
April 18, 2018: Molecular Carcinogenesis
Yue Pan, Jialei Hu, Jia Ma, Xia Qi, Huimin Zhou, Xiaoyan Miao, Wei Zheng, Li Jia
Tumor metastasis is a major cause of cancer-related death in renal cell carcinoma (RCC). MicroRNAs (miRNAs) have been widely known to modulate proliferation invasion, metastasis and apoptosis of cancer cells. In this study, we aimed to investigate the function and novel target of miR-193a-3p and miR-224 in RCC. The levels of miR-193a-3p and miR-224 were significantly increased in RCC tissues and RCC cell lines. Alpha-2, 3-Sialyltransferase IV (ST3GalIV) was highly expressed in adjacent nontumor tissues and human normal proximal tubular cell line HK-2 compared to RCC tissues and cell lines...
April 18, 2018: Molecular Carcinogenesis
Yang Cheng, Yun Zhu, Wanfu Xu, Jiajia Xu, Min Yang, Peiyu Chen, Junhong Zhao, Lanlan Geng, Sitang Gong
Tumor associated macrophages are potential targets of the immune therapy for patients with colon cancer. PKCα acts as a tumor suppressor in the intestine. However, the correlation between PKCα expressed in colon cancer cells and tumor associated macrophages polarization has never been detected. In the present study, the correlation between PKCα expression and level of M1 macrophages was evaluated in human colon cancer tissues. A xenograft mouse model of colon cancer cells with different PKCα expression level was constructed to evaluate the effect of PKCα on M1 macrophages polarization in vivo...
April 10, 2018: Molecular Carcinogenesis
Xueyao Song, Zhiyao Yuan, Hua Yuan, Lihua Wang, Pei Ji, Guangfu Jin, Juncheng Dai, Hongxia Ma
Autophagy is an essential process to maintain cellular homeostasis and functions, which has been demonstrated to play an important role in the different stages of tumorigenesis. To evaluate whether the genetic variants in autophagy-related genes influence the head and neck squamous cell carcinoma (HNSCC) risk, we conducted a case-control study to analyze 11 tagging single nucleotide polymorphisms (SNPs) of three core autophagosome formation genes(ATG5, ATG12 and ATG16L1) with 576 HNSCC cases and 1552 healthy controls among Chinese population...
April 10, 2018: Molecular Carcinogenesis
Liying Wang, Hongfeng Zhang, Jiaxin Zheng, Xiaoli Wei, Jingwen Du, Haibo Lu, Qiuying Sun, Weiyu Zhou, Rui Zhang, Yu Han
Gefitinib exhibits very limited efficacy in gastric cancer (GC). Indeed, the limited clinical results obtained with gefitinib alone justify investigation of additional therapeutic strategies. Here, we demonstrate the importance of EGFR and HER2 in GC malignancy using RNA interference (RNAi). Additionally, we explored the ability of RNAi targeting EGFR and HER2 to enhance the sensitivity of GC cells to gefitinib. Specific small interfering RNAs (siRNAs) significantly inhibited mRNA and protein expression of target genes...
April 10, 2018: Molecular Carcinogenesis
Kristan H Cleveland, Steven Yeung, Kevin M Huang, Sherry Liang, Bradley T Andresen, Ying Huang
Recent studies suggest that the β-blocker drug carvedilol prevents skin carcinogenesis but the mechanism is unknown. Carvedilol is one of a few β-blockers identified as biased agonist based on an ability to promote β-arrestin-mediated processes such as ERK phosphorylation. To understand the role of phosphoproteomic signaling in carvedilol's anticancer activity, the mouse epidermal JB6 P+ cells treated with EGF, carvedilol or their combination were analyzed using the Phospho Explorer Antibody Array containing 1318 site-specific and phospho-specific antibodies of over 30 signaling pathways...
April 6, 2018: Molecular Carcinogenesis
Jie Shen, Renduo Song, Tiffany R Hodges, Amy B Heimberger, Hua Zhao
Circulating metabolomics profiling holds prognostic potential. However, such efforts have not been extensively carried out in glioblastoma. In this study, two-step (training and testing) metabolomics profiling was conducted from the plasma samples of 159 glioblastoma patients. Metabolomics profiling was tested for correlation with 2-year overall and disease-free survivals. Arginine, methionine, and kynurenate levels were significantly associated with 2-year overall survival in both the training and testing sets...
March 30, 2018: Molecular Carcinogenesis
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