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Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes
Eleonora A. Braga1*†, Marina V. Fridman2†, Vitaly I. Loginov1,3, Alexey A. Dmitriev4 and Sergey G. Morozov1
1Institute of General Pathology and Pathophysiology, Moscow, Russia
2Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia
3Research Center of Medical Genetics, Moscow, Russia
4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search f...
Source: Frontiers in Genetics - April 23, 2019 Category: Genetics & Stem Cells Source Type: research
Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD.
Introduction
Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research
High-Throughput Characterization of Viral and Cellular Protein Expression Patterns During JC Polyomavirus Infection
Discussion
The study of viral infections in vitro has provided innumerable advances to the field of virology. However, the lack of rapid and efficient screening tools has hindered research progress for some viruses, like JCPyV (Houff et al., 1983; Zu Rhein, 1983; Assetta and Atwood, 2017). To overcome this challenge, the development of high-throughput analyses is needed to help aid in the production of large data sets and generation of multiple lines of inquiry. Current methodologies for analyzing JCPyV infectivity predominantly rely on manual quantitation of infection by indirect immunodetection of viral proteins by epif...
Source: Frontiers in Microbiology - April 16, 2019 Category: Microbiology Source Type: research
Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals.
Author Contributions
LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 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
The Functions of Non-coding RNAs in rRNA Regulation
Qi Yan1, Chengming Zhu1, Shouhong Guang1,2* and Xuezhu Feng1*
1Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China
2CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Hefei, China
Ribosomes are ribonucleoprotein machines that decode the genetic information embedded in mRNAs into polypeptides. Ribosome biogenesis is tightly coordinated and controlled from the transcription of pre-rRNAs to the assembly of ribosomes. Defects or disorders in rRNA production result in a number of human ri...
Source: Frontiers in Genetics - April 4, 2019 Category: Genetics & Stem Cells Source Type: research
MAP kinase and autophagy pathways cooperate to maintain RAS mutant cancer cell survival Medical Sciences
Oncogenic mutations in the small GTPase KRAS are frequently found in human cancers, and, currently, there are no effective targeted therapies for these tumors. Using a combinatorial siRNA approach, we analyzed a panel of KRAS mutant colorectal and pancreatic cancer cell lines for their dependency on 28 gene nodes that...
Source: Proceedings of the National Academy of Sciences - March 4, 2019 Category: Science Authors: Chih-Shia Lee, Liam C. Lee, Tina L. Yuan, Sirisha Chakka, Christof Fellmann, Scott W. Lowe, Natasha J. Caplen, Frank McCormick, Ji Luo Tags: PNAS Plus Source Type: research
Dicer functions transcriptionally and posttranscriptionally in a multilayer antiviral defense Microbiology
In antiviral RNA interference (RNAi), Dicer plays a primary role in processing double-stranded RNA (dsRNA) molecules into small-interfering RNAs (siRNAs) that guide Argonaute effectors to posttranscriptional suppression of target viral genes. Here, we show a distinct role for Dicer in the siRNA-independent transcriptional induction of certain host genes upon viral...
Source: Proceedings of the National Academy of Sciences - February 5, 2019 Category: Science Authors: Ida Bagus Andika, Hideki Kondo, Nobuhiro Suzuki Tags: PNAS Plus Source Type: research
Erroneous ribosomal RNAs promote the generation of antisense ribosomal siRNA Genetics
Ribosome biogenesis is a multistep process, during which mistakes can occur at any step of pre-rRNA processing, modification, and ribosome assembly. Misprocessed rRNAs are usually detected and degraded by surveillance machineries. Recently, we identified a class of antisense ribosomal siRNAs (risiRNAs) that down-regulate pre-rRNAs through the nuclear RNAi pathway. To...
Source: Proceedings of the National Academy of Sciences - October 2, 2018 Category: Science Authors: Chengming Zhu, Qi Yan, Chenchun Weng, Xinhao Hou, Hui Mao, Dun Liu, Xuezhu Feng, Shouhong Guang Tags: Biological Sciences Source Type: research
Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing Genetics
Epigenetic silencing can be mediated by various mechanisms, and many regulators remain to be identified. Here, we report a genome-wide siRNA screening to identify regulators essential for maintaining gene repression of a CMV promoter silenced by DNA methylation. We identified CSE1L (chromosome segregation 1 like) as an essential factor for...
Source: Proceedings of the National Academy of Sciences - April 24, 2018 Category: Science Authors: Qiang Dong, Xiang Li, Cheng-Zhi Wang, Shaohua Xu, Gang Yuan, Wei Shao, Baodong Liu, Yong Zheng, Hailin Wang, Xiaoguang Lei, Zhuqiang Zhang, Bing Zhu Tags: PNAS Plus Source Type: research
Toward new design principles for superior gene silencing Engineering
Delivery Is the Key Challenge in siRNA Therapies RNA interference (RNAi) or “gene silencing” is a fascinating mechanism in which a cell utilizes a gene’s own RNA sequence to shut down expression of that gene. This process can be employed to investigate the role of genes in disease and to...
Source: Proceedings of the National Academy of Sciences - March 27, 2018 Category: Science Authors: Rangaramanujam M. Kannan Tags: Commentaries Source Type: research
Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference Engineering
Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi) toward clinical translation requires efficient formation of RNA-induced gene-silencing complex (RISC) in the cytoplasm. Here we...
Source: Proceedings of the National Academy of Sciences - March 20, 2018 Category: Science Authors: Jiahe Li, Connie Wu, Wade Wang, Yanpu He, Elad Elkayam, Leemor Joshua-Tor, Paula T. Hammond Tags: PNAS Plus Source Type: research
Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis
This study was funded by the Academy of Finland and by Tekes: Finnish Funding Agency for Innovation. The authors have no conflict of interest to declare.
Source: Human Reproduction - February 15, 2018 Category: Reproduction Medicine Source Type: research
Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing Engineering
Clinical translation of therapies based on small interfering RNA (siRNA) is hampered by siRNA's comprehensively poor pharmacokinetic properties, which necessitate molecule modifications and complex delivery strategies. We sought an alternative approach to commonly used nanoparticle carriers by leveraging the long-lived endogenous serum protein albumin as an siRNA carrier. We synthesized...
Source: Proceedings of the National Academy of Sciences - August 8, 2017 Category: Science Authors: Samantha M. Sarett, Thomas A. Werfel, Linus Lee, Meredith A. Jackson, Kameron V. Kilchrist, Dana Brantley-Sieders, Craig L. Duvall Tags: PNAS Plus Source Type: research
Regulation of claudin ‐4 via p63 in human epithelial cells
P63 is a regulator of cell–cell junction complexes in the epidermis. Claudin‐4 is regulated via various factors in normal epithelial cells and diseases. We found that claudin‐4 was directly regulated via p63 (TAp63 and ΔNp63) in human keratinocytes and nasal epithelial cells. In the epidermis of atopic dermatitis (AD), which contains ΔNp63‐deficient keratinocytes, high expression of claudin‐4 was observed. In primary keratinocytes, downregulation of ΔNp63 by treatment with short interfering RNA (siRNA)‐p63 induced claudin‐4 expression. In nasal epithelial cells in the context of rhinitis or nasal polyps, u...
Source: Annals of the New York Academy of Sciences - July 1, 2017 Category: Science Authors: Takashi Kojima, Takayuki Kohno, Terufumi Kubo, Yakuto Kaneko, Takuya Kakuki, Akito Kakiuchi, Makoto Kurose, Ken ‐ichi Takano, Noriko Ogasawara, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Takumi Konno, Shingo Ichimiya, Tetsuo Himi Tags: REVIEW Source Type: research
