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Inhibition of SMYD2 Sensitized Cisplatin to Resistant Cells in NSCLC Through Activating p53 Pathway
In conclusion, the present study elucidated that the activity of SMYD2 in NSCLC may affect the cell sensitivity to chemotherapeutic agents, especially to CDDP. The elevated SMYD2 mediated CDDP resistance and malignant phenotype in NSCLC, indicating that SMYD2 may be a useful biomarker of CDDP resistance in NSCLC. Inhibition of SMYD2 contributes to the methylation-related activation of p53 and thus results in cell apoptosis. Furthermore, combination treatment with CDDP and an SMYD2 inhibitor had a synergistically antitumor effects in a xenograft model in vivo. Given that SMYD2 has reversible effects and is a targetable prot...
Source: Frontiers in Oncology - April 25, 2019 Category: Cancer & Oncology Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

lncRNA ZEB1-AS1 Mediates Oxidative Low-Density Lipoprotein-Mediated Endothelial Cells Injury by Post-transcriptional Stabilization of NOD2
Conclusion We report the discovery that ZEB1-AS1 functionally participates in ox-LDL-induced ECs injury via LRPPRC-mediated stabilization of NOD2. Uncovering the precise role of ZEB1-AS1/LRPPRC/NOD2 pathway in the progression of ox-LDL-induced ECs death and AS will not only increase our knowledge of ox-LDL-induced AS, but also enable the development of novel therapeutic strategies to overcome oxidation product-induced diseases. Author Contributions XX and CL designed and mainly did the study. CM, ZD, and YD helped and did the study. Conflict of Interest Statement The authors declare that the research was conducted in ...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

Cancers, Vol. 14, Pages 3162: Knockdown of 15-bp Deletion-Type v-raf Murine Sarcoma Viral Oncogene Homolog B1 mRNA in Pancreatic Ductal Adenocarcinoma Cells Repressed Cell Growth In Vitro and Tumor Volume In Vivo
In this study, siRNA was designed for the targeted knockdown of 15-bp deletion-type BRAF mRNA. This siRNA repressed the phosphorylation of extracellular-signal-regulated kinase proteins downstream of BRAF and suppressed cell growth in vitro and in vivo. Furthermore, siRNAs with 2′-O-methyl modifications at positions 2–5 reduce the seed-dependent off-target effects, as confirmed by reporter and microarray analyses. Thus, such siRNA is a promising candidate therapy for 15-bp deletion-type BRAF-induced tumorigenesis.
Source: Cancers - June 28, 2022 Category: Cancer & Oncology Authors: Jiaxuan Song Yoshiaki Kobayashi Yoshimasa Asano Atsushi Sato Hiroaki Taniguchi Kumiko Ui-Tei Tags: Article Source Type: research

The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Exportin 1 (XPO1) inhibition leads to restoration of tumor suppressor miR-145 and consequent suppression of pancreatic cancer cell proliferation and migration.
In this study, we found that the expression of miR-145 was significantly lower in PDAC cells when compared to normal pancreatic duct epithelial cells. Here we show that inhibition of the nuclear exporter protein exportin 1 (XPO1; also known as chromosome maintenance region 1 [CRM1]) by siRNA knockdown or by the Selective Inhibitor of Nuclear Export (SINE) compound (KPT-330; selinexor) increases miR-145 expression in PDAC cells resulting in the decreased cell proliferation and migration capacities. A similar result was obtained with forced expression of miR-145 in PDAC cells. To this end, SINE compound treatment mediated th...
Source: Oncotarget - July 29, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Epigenetic Targeting DNMT1 of Pancreatic Ductal Adenocarcinoma using interstitial control release biodegrading polymer reduced tumor growth through Hedgehog pathway inhibition
Publication date: Available online 29 October 2018Source: Pharmacological ResearchAuthor(s): Mao-Hsuan Huang, Yi-Wen Chou, Ming-Hsun Li, Tina E. Shih, Shinn-Zong Lin, Hong-Meng Chuang, Tzyy-Wen Chiou, Hong-Lin Su, Horng-Jyh HarnAbstractAnnually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the ...
Source: Pharmacological Research - October 30, 2018 Category: Drugs & Pharmacology Source Type: research

Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin
Conclusion: Our results provide novel evidence that HDGF interacts with DDX5 and promotes the progression of EC through the induction of β-catenin. Introduction Endometrial cancer (EC) comprises the most common malignancy involving the female genital tract and the fourth most common malignancy in women after breast, lung, and colorectal cancers (1). In 2012, approximately 320,000 new cases of EC were diagnosed worldwide and the incidence is increasing (2). Currently, endometrial carcinogenesis is thought to be a multi-step process involving the coordinated interaction of hormonal regulation, gene mutation, ad...
Source: Frontiers in Oncology - April 10, 2019 Category: Cancer & Oncology Source Type: research