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Molecular Carcinogenesis

Xiaomeng Xie, Xueyin Zu, Feifei Liu, Ting Wang, Xiangyu Wang, Hanyong Chen, Kangdong Liu, Penglei Wang, Fangfang Liu, Yan Zheng, Ann M Bode, Zigang Dong, Dong Joon Kim
Purpurogallin is a natural compound that is extracted from nutgalls and oak bark and it possesses antioxidant, anticancer, and anti-inflammatory properties. However, the anticancer capacity of purpurogallin and its molecular target have not been investigated in esophageal squamous cell carcinoma (ESCC). Herein, we report that purpurogallin suppresses ESCC cell growth by directly targeting the mitogen-activated protein kinase kinase 1/2 (MEK1/2) signaling pathway. We found that purpurogallin inhibits anchorage-dependent and -independent ESCC growth...
May 17, 2019: Molecular Carcinogenesis
Douglas G Osborne, Joanne Domenico, Yuchun Luo, Anna L Reid, Carol Amato, Zili Zhai, Dexiang Gao, Melanie Ziman, Charles A Dinarello, William A Robinson, Mayumi Fujita
Immune suppression is one of the 10 hallmarks of cancer. Interleukin-37 (IL-37), a member of the IL-1 family, inhibits both innate and adaptive immunity, and has been shown to modulate immune responses in various disease conditions. Yet, IL-37 has rarely been investigated in cancer patients, and its biological role in cancer remains to be elucidated. In this study, we investigated the gene expression of IL-37 in age- and sex-matched blood samples of healthy individuals and melanoma patients, and demonstrated upregulation of IL-37 messenger RNA (mRNA) in the blood samples of melanoma patients...
May 16, 2019: Molecular Carcinogenesis
Eunhye Lee, Taeyun A Lee, Hye Jin Yoo, Sungwook Lee, Boyoun Park
Cellular nucleic acid-binding protein (CNBP) is associated with cell proliferation, and its expression is elevated in human tumors, but the molecular mechanisms of CNBP in tumor cell biology have not been fully elucidated. In this study, we report that CNBP is a transcription factor essential for regulating matrix metalloproteinases mmp-2, mmp-14, and transcription factor e2f2 gene expression by binding to their promoter regions via a sequence-specific manner. Importantly, epidermal growth factor stimulation is required to induce CNBP phosphorylation and nuclear transport, thereby promoting the expression of mmp-2, mmp-14, and e2f2 genes...
May 13, 2019: Molecular Carcinogenesis
Lingyuan Xu, Sensen Qiu, Lehe Yang, Haitang Xu, Xu Liu, Shiqian Fan, Ri Cui, Weitao Fu, Chengguang Zhao, Liqun Shen, Liangxing Wang, Xiaoying Huang
Lung cancer is a leading cause of cancer-related death worldwide. Cyanopyridines and aminocyanopyridines with carbon-nitrogen bonds have been proved to exert significant anticancer, antibacterial, and anti-inflammatory effects. In this study, we showed that aminocyanopyridine 3o and 3k displaying potent antitumor activity via inhibiting the signal transducer and activator of transcription 3 (STAT3) pathway. They blocked the constitutive STAT3 phosphorylation in a dose- and time-dependent manner and regulated the transcription of STAT3 target genes encoding apoptosis factors...
May 8, 2019: Molecular Carcinogenesis
Chunbin Zhang, Fang Han, Ming Shi, Haoxiu Sun, Yiqun Li, Yanpeng Ci, Yuanfei Yao, Peng Dou, Muhammad Luqman Akhtar, Huan Nie, Jie He, Yu Li
Previous investigations have found that MARVEL domain-containing 1 (MARVELD1) could inhibit tumor cell proliferation and enhance the sensitivity to chemotherapeutic drugs in hepatocellular carcinoma. Hence, it may be a valuable therapeutic target. In the study, we analyzed the responsive changes of MARVELD1 to 25 stress factors and expression of MARVELD1 in epithelial tumors of the reproductive system. We found that MARVELD1 was transferred to the cytoplasm and mitochondria under cell stress. And under cellular stress, the reactive oxygen species (ROS) levels decreased in MARVELD1 expressed cells while increased in the cells of MARVELD1-specific siRNA treatment...
May 7, 2019: Molecular Carcinogenesis
Thomas R Holmes, Shravya Dindu, Laura A Hansen
Aberrant subcellular localization of signaling proteins can provide cancer cells with advantages such as resistance to apoptotic cell death, increased invasiveness and more rapid proliferation. Nuclear to cytoplasmic shifts in tumor-promoting proteins can lead to worse patient outcomes, providing opportunities to target cancer-specific processes. Herein, we review the significance of dysregulated protein localization with a focus on skin cancer. Altered localization of signaling proteins controlling cell cycle progression or cell death is a common feature of cancer...
May 6, 2019: Molecular Carcinogenesis
Jeffrey M Peters, Dae J Kim, Moses T Bility, Michael G Borland, Bokai Zhu, Frank J Gonzalez
Considerable progress has been made during the past 20 years towards elucidating the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer. In 1999, the original notion that PPARβ/δ was involved with epithelial cell function was postulated based on a correlation between PPARβ/δ expression and the induction of messenger RNAs encoding proteins that mediate terminal differentiation in keratinocytes. Subsequent studies definitively revealed that PPARβ/δ could induce terminal differentiation and inhibit proliferation of keratinocytes...
May 6, 2019: Molecular Carcinogenesis
Eric T Sugarman, Gao Zhang, Jerry W Shay
Engaging a telomere maintenance mechanism during DNA replication is essential for almost all advanced cancers. The conversion from normal and premalignant somatic cells to advanced malignant cells often results (85%-90%) from the reactivation of the functional ribonucleoprotein holoenzyme complex, referred to as telomerase. Modulation of the human telomerase reverse transcriptase (hTERT) appears to be rate limiting to produce functional telomerase and engage a telomere maintenance mechanism. The remaining 10% to 15% of cancers overcome progressively shortened telomeres by activating an alternative lengthening of telomeres (ALT) maintenance mechanism, through a DNA recombination pathway...
May 6, 2019: Molecular Carcinogenesis
Veronica M Henderson, Ohuod Hawsawi, Liza J Burton, Taaliah Campbell, Kennedi Trice, Jodi Dougan, Simone M Howard, Valerie A Odero-Marah
Prostate cancer (PCa) patients' mortality is mainly attributed to complications caused by metastasis of the tumor cells to organs critical for survival, such as bone. We hypothesized that PCa cell-bone interactions would promote paracrine signaling. A panel of PCa cell lines were cocultured with hydroxyapatite ([HA]; inorganic component of bone) of different densities. Conditioned media (CM) was collected and analyzed for calcium levels and effect on paracrine signaling, cell migration, and viability in vitro and in vivo...
May 2, 2019: Molecular Carcinogenesis
Huaxin Liang, Zhuo Chen, Libo Sun
Glioblastoma (GBM) is one of the major causes of brain cancer-related mortality worldwide. Temozolomide (TMZ) is an important agent against GBM. Acquired TMZ-resistance severely limits the chemotherapeutic effect and leads to poor GBM patient survival. To study the underlying mechanism of drug resistance, two TMZ resistant GBM cell lines, A172 and U87, were generated. In this study, the TMZ resistant cells have less apoptosis and cell-cycle change in response to the TMZ treatment. Western blot results revealed that cyclin E1 was upregulation in TMZ resistant cells...
May 2, 2019: Molecular Carcinogenesis
Fiona Chalmers, Saie Mogre, Jeongin Son, Nicholas Blazanin, Adam B Glick
Cancer is associated with a number of conditions such as hypoxia, nutrient deprivation, cellular redox, and pH changes that result in accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) and trigger a stress response known as the unfolded protein response (UPR). The UPR is a conserved cellular survival mechanism mediated by the ER transmembrane proteins activating transcription factor 6, protein kinase-like endoplasmic reticulum kinase, and inositol-requiring enzyme 1α (IRE1α) that act to resolve ER stress and promote cell survival...
April 30, 2019: Molecular Carcinogenesis
Zhenzhen Zhang, Weixing Yu, Min Zheng, Xinhua Liao, Jichuang Wang, Dayun Yang, Wenxian Lu, Long Wang, Sheng Zhang, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Gastric cancer is the second leading cause of cancer-related mortality and the fourth most common cancer globally. High intratumor heterogeneity of advanced gastric cancer poses great challenges to targeted therapy due to simultaneous activation of many redundant cancer-driving pathways. A central common signaling mechanism in cancer is proline-directed phosphorylation, which is further regulated by the unique proline isomerase Pin1. Pin1 inhibition exerts anticancer activity by blocking multiple cancer-driving pathways in some cancers, but its role in gastric cancer is not fully understood...
April 26, 2019: Molecular Carcinogenesis
Qi Sun, Yuzhuo Wang, Jingyi Fan, Zhihua Li, Jiahui Zhang, Lijuan Wang, Xikang Fan, Mengmeng Ji, Meng Zhu, Juncheng Dai, Hongxia Ma, Guangfu Jin, Zhibin Hu, Hongbing Shen
Identification of long noncoding RNA (lncRNA) expression quantitative trait loci (lncR-eQTL) that associated with lung cancer can provide insights into regulatory mechanisms of lncRNA, and help reveal the role of lncRNA in lung cancer. A two-stage case-control design was implemented in this study. We first selected the lncRNAs that differently expressed based on the Cancer Genome Atlas (TCGA) project (75 normal and 708 tumor tissues) and identified eQTLs for selected lncRNAs based on data of 278 normal lung tissues from the the genotype-tissue expression database...
April 26, 2019: Molecular Carcinogenesis
Hao Peng, Hao Li
The present investigation was intended to elucidate whether long noncoding RNA small nuclear RNA host gene 16 (SNHG16) could regulate the epithelial-mesenchymal transition process of bladder cancer cells by directing expressions of miR-17-5p and metalloproteinases 3 (TIMP3). To elucidate the point, we collected 275 pairs of bladder cancer tissues and corresponding adjacent normal tissues, as well as four bladder cancer cell lines and the normal human bladder epithelial cell line. Moreover, pcDNA3.1-SNHG16, si-SNHG16, miR-17-5p mimic, miR-17-5p inhibitor, pcDNA3...
April 26, 2019: Molecular Carcinogenesis
Sally E Dickinson, Georg T Wondrak
The health and economic burden imposed by skin cancer is substantial, creating an urgent need for the development of improved molecular strategies for its prevention and treatment. Cutaneous exposure to solar ultraviolet (UV) radiation is a causative factor in skin carcinogenesis, and TLR4-dependent inflammatory dysregulation is an emerging key mechanism underlying detrimental effects of acute and chronic UV exposure. Direct and indirect TLR4 activation, upstream of inflammatory signaling, is elicited by a variety of stimuli, including pathogen-associated molecular patterns (such as lipopolysaccharide) and damage-associated molecular patterns (such as HMGB1) that are formed upon exposure to environmental stressors, such as solar UV...
April 24, 2019: Molecular Carcinogenesis
Jacob New, Dharmalingam Subramaniam, Satish Ramalingam, Jonathan Enders, Afreen Asif Ali Sayed, Sivapriya Ponnurangam, David Standing, Prabhu Ramamoorthy, Maura O'Neil, Dan A Dixon, Subhrajit Saha, Shahid Umar, Sumedha Gunewardena, Roy A Jensen, Sufi Mary Thomas, Shrikant Anant
We previously reported that ionizing radiation (IR) mediates cell death through the induction of CUGBP elav-like family member 2 (CELF2), a tumor suppressor. CELF2 is an RNA binding protein that modulates mRNA stability and translation. Since IR induces autophagy, we hypothesized that CELF2 regulates autophagy-mediated colorectal cancer (CRC) cell death. For clinical relevance, we determined CELF2 levels in The Cancer Genome Atlas (TCGA). Role of CELF2 in radiation response was carried out in CRC cell lines by immunoblotting, immunofluorescence, autophagic vacuole analyses, RNA stability assay, quantitative polymerase chain reaction and electron microscopy...
April 24, 2019: Molecular Carcinogenesis
Sharad S Singhal, David Horne, Jyotsana Singhal, Steven Vonderfecht, Ravi Salgia, Sanjay Awasthi
Substantial evidence suggests that 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinogenesis in mice mimics human breast cancer (BC) in many respects. Therefore, it has been used extensively to evaluate preventive and therapeutic agents for human BC. Mammary carcinogenesis induced by DMBA administration in female SENsitive to CARcinogen (SENCAR) mice was characterized by histopathological analysis of the mammary glands and alterations to the phosphatidylinositol 3-kinase/protein kinase B/cyclin-dependent kinase 1 (PI3K/Akt/CDK1) pathway...
April 21, 2019: Molecular Carcinogenesis
Neha Jain, Jyoti Roy, Basudeb Das, Bibekanand Mallick
The abnormal expressions of microRNAs (miRNAs) are known to be associated with various pathophysiological processes that lead to the development of a plethora of diseases including cancer. Among several miRNAs studied so far, miR-197 has been reported to play a vital role either as an oncogene or tumor suppressor in different cancers. However, its role in carcinogenesis of fibrosarcoma has not yet been elucidated. Therefore, the current study investigated the role of miR-197-5p, which is significantly downregulated in HT1080 fibrosarcoma cells compared to IMR90-tert fibroblast cells...
April 18, 2019: Molecular Carcinogenesis
Ke Wang, Xingchen Yu, Hongwei Jiang, Jiao Huang, Huanzhuo Wang, Hongyu Jiang, Sheng Wei, Li Liu
Genetic factors play important roles in colorectal carcinogenesis. This study was aimed to evaluate the effects of gene expression-related copy number variations (CNVs) on the risk of colorectal cancer in Chinese. Expression Quantitative Trait Locus (eQTL) mapping was conducted to explore the most regulatable gene expressions by CNVs among the whole genome based on publicly available data. Then a case-control study was performed to evaluate the associations between copy numbers of the most regulatable genes and colorectal cancer...
April 18, 2019: Molecular Carcinogenesis
Xinyuan Xu, Danwen Qian, Hongliang Liu, Diana Cruz, Sheng Luo, Kyle M Walsh, James L Abbruzzese, Xuefeng Zhang, Qingyi Wei
The liver kinase B1-AMP-activated protein kinase (LKB1-AMPK) pathway has been identified as a new target for cancer therapy, because it controls the glucose and lipid metabolism in response to alterations in nutrients and intracellular energy levels. In the present study, we aimed to identify genetic variants of the LKB1-AMPK pathway genes and their associations with pancreatic cancer (PanC) risk using 15 418 participants of European ancestry from two previously published PanC genome-wide association studies...
April 17, 2019: Molecular Carcinogenesis
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