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Gene targeting

Linas Tamošaitis, C Mark Smales
Transcriptomics has been extensively applied to the investigation of the CHO cell platform for the production of recombinant biotherapeutic proteins to identify transcripts whose expression is regulated and correlated to (non)desirable CHO cell attributes. However, there have been few attempts to analyse the findings across these studies to identify conserved changes and generic targets for CHO cell platform engineering. Here we have undertaken a meta-analysis of CHO cell transcriptomic data and report on those genes most frequently identified as differentially expressed with regard to cell growth (µ) and productivity (Qp)...
June 19, 2018: Biotechnology Journal
Go Shinke, Daisaku Yamada, Hidetoshi Eguchi, Yoshifumi Iwagami, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Koichi Kawamoto, Kunihito Gotoh, Shogo Kobayashi, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki
Current therapies for pancreatic ductal cancer (PDAC) do not sufficiently control distant metastasis. Thus, new therapeutic targets are urgently needed. Numerous studies have suggested that the epithelial-mesenchymal transition (EMT) is pivotal for metastasis of carcinomas. The fact that the EMT is reversible suggests the possibility that it is induced by an epigenetic mechanism. In this study, we aimed to investigate the role of histone deacetylase 1 (HDAC1), which is an epigenetic mechanism on distant metastasis of PDAC...
June 19, 2018: Cancer Science
L-J Hou, J-J Han, Y Liu
OBJECTIVE: The present study is aimed to investigate the regulatory effect of microRNA (miRNA or miR)-503 on endothelial functions, as well as the mechanism by which high glucose leads to injury of endothelial cells. MATERIALS AND METHODS: When reaching 80% confluency, human umbilical vein endothelial cells (HUVECs) were subjected to non-serum synchronization for 12 h, and medium of cells in high-glucose (HG) group was replaced by normal medium supplemented with 25 mmol/L D-glucose...
June 2018: European Review for Medical and Pharmacological Sciences
M A Bakhrebah, M S Nassar, M S Alsuabeyl, W A Zaher, S A Meo
OBJECTIVE: Infectious diseases are one of the prime causes of death worldwide. An innovative sequence specific editing technology "Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)" has been tested on a broad range of microorganisms to target and destroy invading foreign DNA to human cells or tissues. This study aimed to discuss the mechanism and therapeutic usage of CRISPR/Cas9 genome editing technology in the management of various infectious disease pathogens...
June 2018: European Review for Medical and Pharmacological Sciences
Y-T Fu, H-B Zheng, D-Q Zhang, L Zhou, H Sun
OBJECTIVE: To explore the effects of microRNA-1266 (miR-1266) on metastasis and growth in papillary thyroid carcinoma cells and to provide therapeutic targets for papillary thyroid carcinoma. PATIENTS AND METHODS: By quantitative Real-time polymerase chain reaction (PCR), miR-1266 expression level in 38 pairs of papillary thyroid carcinoma tissues and three breast cancer-derived cell lines was examined. After transfection with miR-1266 mimics, the effects of miR-1266 over-expression on cell proliferation, invasion and migration were analyzed...
June 2018: European Review for Medical and Pharmacological Sciences
H-W Qu, Y Jin, Z-L Cui, X-B Jin
OBJECTIVE: To investigate the role of microRNA-212 in prostate cancer (PCa) and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-212 expressions in 72 PCa tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). The relationship between microRNA-212 expression and clinical characteristics of PCa patients was analyzed. Target genes of microRNA-212 were predicted by TargetScan and verified by luciferase reporter gene assay...
June 2018: European Review for Medical and Pharmacological Sciences
B Song, Y-J Tang, W-G Zhang, C-C Wan, Y Chen, L-J Zhang
OBJECTIVE: Extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway is widely involved in cell proliferation and invasion regulation. Enhanced expression or function of ERK1 is important for leukemia. Abnormal down-regulation of microRNA (miR)-143 is correlated with leukemia pathogenesis, indicating possible tumor-suppressing role. Bioinformatics analysis showed the existence of complementary binding sites between miR-143 and ERK1. This study aims to investigate whether the miR-143 plays a role in mediating ERK1 expression and proliferation and apoptosis of leukemia cells...
June 2018: European Review for Medical and Pharmacological Sciences
K Tan, Y-T Peng, P Guo
OBJECTIVE: To investigate the role of miR-29a in regulating the differentiation mesenchymal stem cells into osteoblasts. MATERIALS AND METHODS: For the first step, the changes of expression of miR-29a during the process of mesenchymal stem cells (MSCs) differentiation into osteoblast were detected. Then, we infected the MSCs with mimics or inhibitors of miR-29a to explore the roles of miR-29a in the differentiation. Further, the prediction and verification of the possible target genes of miR-29a were achieved by bioinformatics analysis and luciferase reporter assay...
June 2018: European Review for Medical and Pharmacological Sciences
X-L Gao, M-G Cao, G-G Ai, Y-B Hu
OBJECTIVE: To study effects of microRNA-98 (miR-98) on osteogenic differentiation of mesenchymal stem cells (MSCs). PATIENTS AND METHODS: We predicted target gene of miR-98 with software test, and detected expression changes of miR-98, as well as its target gene HMGA2, in the process of osteogenic differentiation of mesenchymal stem cells. After transfection of miR-98 mimic and HMGA2 siRNA, we induced osteogenic differentiation and detected expression changes of osteogenic differentiation markers (RUNX2, ALP, OCN, and BSP)...
June 2018: European Review for Medical and Pharmacological Sciences
J-B Ge, J-T Lin, H-Y Hong, Y-J Sun, Y Li, C-M Zhang
OBJECTIVE: To investigate whether miR-374b can promote the differentiation of MSCs into osteoblasts by mediating PTEN, thus promoting fracture healing. MATERIALS AND METHODS: Primary cultured mouse mesenchymal stem cells were obtained for following experiments. Flow cytometry was used to determine the expression of MSCs surface antigens to identify the purity. Alizarin red staining was used to detect whether MSCs could differentiate into osteoblasts. QRT-PCR was used to detect the expression of osteogenic marker genes as well as miR-374b and PTEN in bone marrow-derived MSCs from fractured mice model...
June 2018: European Review for Medical and Pharmacological Sciences
Xusheng Ding, Wenqi Xi, Jun Ji, Qu Cai, Jinling Jiang, Min Shi, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Cancer‑associated fibroblasts (CAFs) are predominate cells in tumor stroma and play a key role in tumor progression. Hepatocyte growth factor (HGF) is a cytokine mainly derived from fibroblasts. In the present study, we reported that HGF significantly promoted angiogenesis of human umbilical vein endothelial cells (HUVECs) and vasculogenic mimicry (VM) formation of gastric cancer cells, respectively, by increasing cell proliferation and migration. In addition, mosaic vessels formed by HUVECs and gastric cancer cells were also increased with treatment of recombinant human HGF and conditioned medium from CAFs...
June 18, 2018: Oncology Reports
Susanne Horn, Sonia Leonardelli, Antje Sucker, Dirk Schadendorf, Klaus G Griewank, Annette Paschen
Poor clinical responses to checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies in melanoma have recently been associated with acquired IFNγ resistance that protects tumor cells from the antiproliferative and pro-apoptotic cytokine activity. IFNγ-resistant melanoma cells very often lack functional expression of the IFNγ signaling pathway gene JAK2 due to gene deletions or inactivating gene mutations. Analyzing melanoma cell lines (n = 46, applying next-generation targeted sequencing and single nucleotide polymorphism arrays) as well as available genomic data sets from The Cancer Genome Atlas (TCGA) tumor tissue samples (cutaneous melanoma n = 367, lung squamous cell carcinoma n = 501, bladder urothelial carcinoma n = 408, breast invasive carcinoma n = 768, colorectal adenocarcinoma n = 257), we demonstrate that the frequent chromosomal losses of the tumor suppressor CDKN2A in melanoma and other tumor entities enhance the susceptibility to IFNγ resistance by concomitant deletion of the JAK2 gene (odds ratio = 223...
June 1, 2018: Journal of the National Cancer Institute
Sozaburo Ihara, Yoshihiro Hirata, Yohko Hikiba, Aya Yamashita, Mayo Tsuboi, Masahiro Hata, Mitsuru Konishi, Nobumi Suzuki, Kosuke Sakitani, Hiroto Kinoshita, Yoku Hayakawa, Hayato Nakagawa, Hideaki Ijichi, Keisuke Tateishi, Kazuhiko Koike
Background and Aims: Disturbance of intestinal homeostasis is associated with the development of inflammatory bowel disease (IBD), and TGF-β signaling impairment in mononuclear phagocytes (MPs) causes murine colitis with goblet cell depletion. Here, we examined an organoid-MP co-culture system to study the role of MPs in intestinal epithelial differentiation and homeostasis. Methods: Intestinal organoids were co-cultured with lamina propria leukocytes and bone marrow-derived dendritic cells (BMDCs) from CD11c-cre Tgfbr2fl/fl mice...
June 16, 2018: Journal of Crohn's & Colitis
Yan Xu, Junwen Yang, Fujun Li, Guanghui Lian, Miao Ouyang
Ulcerative colitis (UC), with high morbidity has become one of the fastest-growing severe illnesses in the world. Although MiR-29a is highly expressed in the tissues of UC patients, the mechanism of miR-29a involved in the specific pathogenesis of UC is not known. In this study, a GFP-light chain 3 (LC3) immunofluorescence assay was used to observe the formation of the autophagic spot; qRT-PCR and western blotting analyses were carried out to detect the expression of autophagy-related proteins, including BECN1, Autophagy-related gene (ATG)5, ATG16L, and transcription factor EB...
June 18, 2018: Anti-cancer Drugs
Matthew R Pennington, Jennifer K Grenier, Gerlinde R Van de Walle
Anti-microbial compounds typically exert their action by directly interfering with one or more stages of the pathogen's life cycle. However, some compounds also have secondary effects on the host that aid in pathogen clearance. Raltegravir is a human immunodeficiency virus (HIV)-integrase inhibitor that has been shown to alter the host immune response to HIV in addition to its direct antiviral effect. Interestingly, raltegravir can also directly inhibit the replication of various herpesviruses. However, the host-targeted effects of this drug in the context of a herpesvirus infection have not been explored...
June 19, 2018: Journal of General Virology
Baoyong Wang, Hongwei Chen, Chunfen Zhang, Tian Yang, Qiaofei Zhao, Yifan Yan, Yu Zhang, Feng Xu
Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors. At present, the molecular mechanism of HCC remains unclear. A recent circular RNA (circRNA) profiling study showed that circRBM23 expression was upregulated in HCC tissues. Therefore, in this study, the impact of circRBM23 during the progression of HCC was evaluated. The expression levels of circRBM23 and miR-138 in HCC tissues and HCC cell lines were determined by RT-PCR and the results indicated that circRBM23 expression was increased in the HCC tissues and HCC cell lines, whereas miR-138 expression was decreased...
June 2018: Cancer Biotherapy & Radiopharmaceuticals
Shumei Wang, Yaqi Zhang, Shunping Yuan, Xiaoling Ji
A large body of evidence has indicated that microRNAs (miRNAs/miRs) have essential roles in the development and progression of cervical cancer. Thus, miRNAs with dysregulated expression are potential biomarkers for cervical cancer diagnosis and prognosis. In the present study, expression levels of miR‑485 were detected in cervical cancer tissues and cell lines. The effects of miR‑485 overexpression on the proliferation and invasion of cervical cancer cells were determined with Cell Counting kit‑8 and Transwell invasion assays...
June 18, 2018: Molecular Medicine Reports
Bo Wang, Mujun Yin, Cheng Cheng, Hongpeng Jiang, Kewei Jiang, Zhanlong Shen, Yingjiang Ye, Shan Wang
Growing evidence indicates a potential role for miR‑490‑3p in tumorigenesis. However, its function in colorectal carcinoma (CRC) remains undefined. In this study, miR‑490‑3p was markedly downregulated in fifty colorectal cancer tissue samples compared with the corresponding adjacent non‑cancerous specimens, by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of miR‑490‑3p were closely associated with tumor differentiation and distant metastasis. In addition, both Kaplan-Meier and multivariate analyses indicated CRC patients with elevated miR‑490‑3p amounts had prolonged overall survival...
June 19, 2018: International Journal of Oncology
Tian-Sheng He, Tian Chen, Dan-Dan Wang, Liang-Guo Xu
Mitochondrial anti‑viral signaling protein (VISA), additionally termed MAVS, IPS‑1 and Cardif, is located at the outer membrane of mitochondria and is an essential adaptor in the Rig‑like receptor (RLRs) signaling pathway. Upon viral infection, activated RLRs interact with VISA on mitochondria, forming a RLR‑VISA platform, leading to the recruitment of different TRAF family members, including TRAF3, TRAF2 and TRAF6. This results in the phosphorylation and nuclear translocation of interferon regulatory factors 3 and 7 (IRF3/IRF7) by TANK binding kinase 1 (TBK1) and/or IKKε, as well as activation of NF‑κB, to induce type I interferons (IFNs) and pro‑inflammatory cytokines...
June 15, 2018: Molecular Medicine Reports
Xinmei Luo, Sujuan Ye, Qianqian Jiang, Yi Gong, Yue Yuan, Xueting Hu, Xiaolan Su, Wen Zhu
Wnt inhibitory factor‑1 (WIF‑1) is an important antagonist of Wnt/β‑catenin signaling by binding to Wnt ligands. The downregulation of WIF‑1 leads to the development of non‑small cell lung cancer (NSCLC). The upregulation of WIF‑1 significantly inhibits proliferation and induces apoptosis by inhibiting Wnt/β‑catenin signaling in NSCLC. However, the mechanisms underlying the inhibition of Wnt/β‑catenin signaling by WIF‑1‑mediated autophagy are poorly understood. Thus, in this study, we aimed to shed some light into these mechanisms...
June 15, 2018: International Journal of Oncology
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