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Rnai cancer

Haijing Niu, Yuchen Jia, Tao Li, Bingzhong Su
BACKGROUND: Gastric intestinal metaplasia (IM) is regarded as a premalignant lesion, conferring risks for gastric cancer development. An intestinal transcription factor, CDX2, plays a vital role in establishing and maintaining IM. SOX2, an HMG-box transcription factor, is expressed in normal gastric mucosa and downregulated in IM. Therefore, it is important to elucidate the mutual interaction of SOX2 and CDX2 in gastric IM. AIMS: This study aims to evaluate the negative correlation between SOX2 and CDX2 in mRNA expression and promoter methylation and to illuminate the effect of SOX2 on the promoter methylation of CDX2...
December 2, 2016: Digestive Diseases and Sciences
Agnieszka Sobecka, Wojciech Barczak, Wiktoria Maria Suchorska
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. The treatment of choice in case of head and neck cancer is surgery, followed by chemo- or/and radiotherapy. A potentially effective instrument to improve the outcome of numerous diseases, including viral infections, diabetes and cancer, is RNA interference (RNAi). It has been demonstrated that small interfering RNA and microRNA molecules are strongly involved in the regulation of various different pathological processes in cancer development...
November 2016: Oncology Letters
Dan Shao, Jie Ma, Chao Zhou, Jia-Nan Zhao, Lu-Lu Li, Tong-Jian Zhao, Xi-Lei Ai, Ping Jiao
STAT3 is persistently activated in a wide variety of human tumors, and aberrant STAT3 activity promotes tumor growth, invasion and metastasis. To explore STAT3 down-regulation in human esophageal cancer cells, cell proliferation, apoptosis and mitochondrial mechanisms were explored in esophageal carcinoma TE1 cell cultures. We demonstrate for the first time that STAT3 down-regulation by RNAi is sufficient to inhibit esophageal cancer cell proliferation inducing cell apoptosis. Further, we demonstrate that mitochondrial transmembrane potential is impaired thereby leading to collapsed mitochondrial membrane potential, abnormal mitochondrial membrane depolarization, nuclear DNA fragmentation and cell cycle G2/M arrest under the conditions of STAT3 down-regulation...
November 29, 2016: Clinical and Experimental Pharmacology & Physiology
Yong-Chao Liu, Wen-Hui Ma, Yin-Lin Ge, Mei-Lan Xue, Zheng Zhang, Jin-Yu Zhang, Lin Hou, Run-Hong Mu
Vascular endothelial cell growth factor (VEGF)-C promotes tumorigenesis by allowing lymph node metastasis and lymphangiogenesis, among other actions. RNA interference (RNAi) is a novel technique for suppressing target gene expression and may increase the effectiveness of cancer treatments. The present study assessed the influence of VEGF-C RNAi on the apoptosis and proliferation of mouse breast cancer cells in vitro and in vivo. A total of three pairs of small interfering RNA (siRNA) targeting mouse VEGF-C were designed and synthesized prior to transfection into 4T1 cells via a liposomal approach...
November 2016: Oncology Letters
Weiying Li, Wentao Yue, Hui Wang, Baitang Lai, Xuehui Yang, Chunyan Zhang, Yue Wang, Meng Gu
The objective of the present study was to investigate whether cyclooxygenase-2 (COX-2) is associated with malignancy, and to investigate its molecular mechanisms in human lung cancer tumor malignancy. The present study used RNA interference (RNAi) methodology and celecoxib, a COX-2 inhibitor, to investigate the effect of COX-2 knockdown on the proliferation and invasion abilities of lung cancer cells and the molecular mechanisms involved. Human lung adenocarcinoma A549-si10 and LTEP-A2 cells transfected with a specific small interfering RNA (A549-si10 and LTEP-A2-si10, respectively) grew more slowly compared with parental cell lines and cells transfected with pU6...
November 2016: Oncology Letters
Zhen Yang, Ting Zhou, Yuanchi Cheng, Mingming Li, Xianglin Tan, Feng Xu
Excessive human serum albumin (eHSA) impact on anticancer effects is inconsistent. We explored the outcome of cisplatin (DDP)/etoposide (VP-16) plus eHSA in vivo and in vitro. C57BL/6 mice with tumor were used to compare the efficacy of DDP/VP-16 alone and DDP/VP-16+eHSA. Blood albumin was measured to confirm whether eHSA elevate its level. Western blotting assay were used to measure the expression of ERCC1/TOP2A in tumor tissues. Cell proliferation, mRNA, and protein expression of ERCC1/TOP2A were also assayed to compare two groups in A549 cells...
2016: Frontiers in Pharmacology
Mutian Lv, Yaming Li, Xin Tian, Shundong Dai, Jing Sun, Guojiang Jin, Shenyi Jiang
Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, has been recognized as a critical regulator of various cancers. In this study, we investigated the role of NLK in human small-cell lung cancer (SCLC), which is the most aggressive form of lung cancer. NLK expression was evaluated by quantitative real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi efficiently suppressed NLK expression in NCI-H446 cells, resulting in a significant reduction in cell viability and proliferation in vitro...
2016: Drug Design, Development and Therapy
Swathi V Iyer, Atul Ranjan, Harold K Elias, Alejandro Parrales, Hiromi Sasaki, Badal C Roy, Shahid Umar, Ossama W Tawfik, Tomoo Iwakuma
The ability of cancer cells to survive and grow in anchorage- and serum-independent conditions is well correlated with their aggressiveness. Here, using a human whole-genome shRNA library, we identify TMIGD3 isoform1 (i1) as a factor that suppresses this ability in osteosarcoma (OS) cells, mainly by inhibiting NF-κB activity. Knockdown of TMIGD3 increases proliferation, tumour formation and metastasis of OS cells. Overexpression of TMIGD3 isoform1 (i1), but not isoform3 (i3) which shares a common C-terminal region, suppresses these malignant properties...
November 25, 2016: Nature Communications
Giorgia Adamo, Natascia Grimaldi, Simona Campora, Donatella Bulone, Maria Luisa Bondì, Mohamad Al-Sheikhly, Maria Antonietta Sabatino, Clelia Dispenza, Giulio Ghersi
(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs...
November 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shan Qin, Yanfang Li, Xuexia Cao, Jiexian Du, Xianghua Huang
A key transcription factor associated with poor prognosis and resistance to chemotherapy in ovarian cancer is NANOG. However, the mechanism by which NANOG functions remains undefined. It has been suggested that epithelial to mesenchymal transition (EMT) also contributes to development of drug resistance in different cancers. We thus determined whether NANOG expression was associated with EMT and chemoresistance in epithelial ovarian cancer cells. NANOG expression was increased in epithelial ovarian cancer cell lines compared with its expression in normal epithelial ovarian cell lines...
November 24, 2016: Bioscience Reports
Athanasios Pseftogas, Christos Gonidas, George Mosialos
Several studies have implicated the downregulation of the tumor suppressor Cyld expression in breast cancer development. However, the mechanisms that regulate Cyld expression in mammary epithelial cells are largely unknown. In order to investigate them, a bioinformatic analysis of the promoter region of Cyld was performed and identified putative nuclear hormone receptor response elements that included peroxisome proliferator-activated receptor gamma (PPAR-γ)-responsive elements. In the present study, we showed that upon activation of the nuclear hormone receptor PPAR-γ by the agonist troglitazone (TZD), there was a significant increase in Cyld mRNA in human mammary epithelial cell lines...
November 16, 2016: International Journal of Biochemistry & Cell Biology
Heba Z Sailem, Chris Bakal
The associations between clinical phenotypes (tumour grade, survival), and cell phenotypes, such as shape, signalling activity, and gene expression, are the basis for cancer pathology; but the mechanisms explaining these relationships are not always clear. The generation of large datasets containing information regarding cell phenotypes, and clinical data, provides an opportunity to describe these mechanisms. Here we develop an image-omics approach to integrate quantitative cell imaging data, gene expression, and protein-protein interaction data to systematically describe a 'shape-gene network' that couples specific aspects of breast cancer cell shape to signalling and transcriptional events...
November 18, 2016: Genome Research
Yanan Sun, Xiaopeng Jia, Qiang Gao, Xing Liu, Lianguo Hou
Epithelial to mesenchymal transition (EMT) is an important prerequisite for metastasis to secondary organs. Interleukin-like EMT inducer (ILEI) protein has been shown to translationally upregulated during EMT and metastatic progression as a consequence of aberrant TGF-β signaling. Our initial evaluation of FAM3C (encoding ILEI) and ILEI expression in normal prostate (PCS-440-010) and prostate cancer cell lines (DU145, LNCaP, and PC3) revealed detectable protein expression in only LNCaP cell line even though all cell lines tested had comparable FAM3C expression...
November 10, 2016: IUBMB Life
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Detian Xie, Liang Shang, Lipan Peng, Leping Li
OBJECTIVE: To identify an effective saRNA sequence that can specifically up-regulate VEZT expression and to determine the influence of saRNA had on gastric cancer cell growth, proliferation, invasion and migration. METHODS: Three various saRNAs, that target the VEZT gene promoter at different locations relative to the transcription start site were synthesized. A dsControl saRNA was synthesized as a negative control, and a specific shRNA was synthesized to knockdown VEZT and eliminate any off-target effects of the saRNA...
November 14, 2016: Biochemical and Biophysical Research Communications
K Huang, G Chen, Y Li, J K Liu, Z Y Wang, G C Zhou
Objective: To investigate the expression of p21-activated kinase 1 (PAK1) in bladder cancer and its biological influence on invasion ability of bladder cancer cells. Methods: A total of 54 paraffin-embedded bladder cancer tissue samples and 12 normal bladder tissue specimens were retrieved in Jinshan Hospital Affiliated to Fudan University between January 2009 and December 2012. The expression of PAK1 in these tissues was detected by immunohistochemical staining. The PAK1 mRNA and protein levels were measured in bladder cancer cell lines and human normal bladder epithelial cell line using real-time, fluorescence-based quantitative polymerase chain reaction (RT-PCR) and Western blot, respectively...
November 1, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Neil T Phippen, Nicholas W Bateman, Guisong Wang, Kelly A Conrads, Wei Ao, Pang-Ning Teng, Tracy A Litzi, Julie Oliver, G Larry Maxwell, Chad A Hamilton, Kathleen M Darcy, Thomas P Conrads
BACKGROUND AND OBJECTIVE: Nua kinase 1 (NUAK1) was identified in multigene signatures of survival and suboptimal debulking in high-grade serous ovarian cancer (HGSOC). This study investigates the individual clinical and biologic contributions of NUAK1 in HGSOC patients and cell lines. METHODS: Public transcript expression, clinical, and outcome data were used to interrogate the relationship between NUAK1 and clinicopathologic factors and patient outcomes including progression-free survival (PFS) and molecular subtypes using logistic and Cox modeling...
2016: Frontiers in Oncology
Romi Gupta, Narendra Wajapeyee
Metabolic regulation can play key role in normal and pathological states. In particular in cancer cells, alterations in metabolic pathways can drive the growth and survival of cancer cells. Among these alterations, many occur at the transcriptional level leading to the overexpression of metabolic genes. However, not every metabolically upregulated genes may be necessary for tumor growth. Therefore, functional validation approaches are required to distinguish metabolically overexpressed genes that are necessary for tumor growth versus the ones that are not...
2017: Methods in Molecular Biology
Matteo Forloni, Thuy Ho, Lisha Sun, Narendra Wajapeyee
RNA interference (RNAi) is a powerful research tool that can be used to silence the expression of a specific gene. In the past several years, RNAi has provided the opportunity to identify factors and pathways involved in complex biological processes by performing unbiased loss-of-function screens on a genome-wide scale. Here we describe a genome-wide RNAi screening strategy to identify factors that regulates epigenetic silencing of a specific tumor suppressor gene, using RASSF1A as an example. The approach we describe is a general RNAi screening strategy that can be applied to identify other factors that drive and/or maintain epigenetic modifications on specific genes, including cancer-related genes...
2017: Methods in Molecular Biology
Xueran Chen, Haoran Yang, Shangrong Zhang, Zhen Wang, Fang Ye, Chaozhao Liang, Hongzhi Wang, Zhiyou Fang
Supervillin is an actin-associated protein that regulates actin dynamics by interacting with Myosin II, F-actin, and Cortactin to promote cell contractility and cell motility. Two splicing variants of human Supervillin (SV1 and SV4) have been reported in non-muscle cells; SV1 lacks 3 exons present in the larger isoform SV4. SV2, also called archvillin, is present in striated muscle; SV3, also called smooth muscle archvillin or SmAV, was cloned from smooth muscle. In the present study, we identify a novel splicing variant of Supervillin (SV5)...
November 5, 2016: Biochemical and Biophysical Research Communications
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