scholarly journals Locked nucleic acid-inhibitor of miR-205 decreases endometrial cancer cells proliferation in vitro and in vivo

Oncotarget ◽  
2016 ◽  
Vol 7 (45) ◽  
pp. 73651-73663 ◽  
Author(s):  
Anna Torres ◽  
Joanna Kozak ◽  
Agnieszka Korolczuk ◽  
Dominika Rycak ◽  
Paulina Wdowiak ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Nucleic Acid ◽  
Cancer Cells ◽  
Locked Nucleic Acid ◽  
Acid Inhibitor ◽  
Proliferation In Vitro

scholarly journals In vitro and in vivo activity of miR-92a–Locked Nucleic Acid (LNA)–Inhibitor against endometrial cancer

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Anna Torres ◽  
Joanna Kozak ◽  
Agnieszka Korolczuk ◽  
Paulina Wdowiak ◽  
Ewa Domańska-Glonek ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Nucleic Acid ◽  
Locked Nucleic Acid

scholarly journals Erratum to: In vitro and in vivo activity of miR-92a–Locked Nucleic Acid (LNA)–Inhibitor against endometrial cancer

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Anna Torres ◽  
Joanna Kozak ◽  
Agnieszka Korolczuk ◽  
Paulina Wdowiak ◽  
Ewa Domańska-Glonek ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Nucleic Acid ◽  
Locked Nucleic Acid

932 Targeting the 19S Proteasomal Subunit, Rpt4, in Colon Cancer Cells Induces Cell Death and Reduces Cellular Proliferation In Vitro and In Vivo

2013 ◽  
Vol 144 (5) ◽  
pp. S-166-S-167
Author(s):  
Karen Boland ◽  
Caoimhin Concannon ◽  
Niamh McCawley ◽  
Elaine W. Kay ◽  
Deborah McNamara ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Colon Cancer Cells ◽  
Proliferation In Vitro

siRNA Versus Antisense Locked Nucleic Acids: Stay Single!.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 614-614
Author(s):  
Phil Kearney ◽  
Majken Westergaard ◽  
Henrik F. Hansen ◽  
Ellen M. Staarup ◽  
Troels Koch ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Locked Nucleic Acid ◽  
Target Validation ◽  
Host Animal ◽  
Clinical Phase ◽  
Potent Inhibition

Abstract Much discussion has centred around the utility and benefits of siRNA in both target validation and as a therapeutic option. This has been driven by significant publications including that of Soutcheck et al (Nature432, 173–177 2004), which demonstrated liver targeting as well as in vivo efficacy when siRNA against ApoB was tethered to a cholesterol moiety. Santaris Pharma has developed a third generation nucleic acid chemistry referred to as locked nucleic acid (LNA) which delivers unmatched affinity and stabiliy benefits, largely overcoming the drawbacks associated with traditional antisense molecules. We therefore sought to compare this chemistry with targets which siRNA has been successfully used in in vivo/in vitro settings. The same motif used in the Soutcheck study was targeted with a LNA molecule, and the free siRNA activity was compared to the cholesterol linked and free LNA molecules in their ability ot down regulate ApoB expression. LNA (SPC3197) inhibited ApoB expression by 90% while at an equimolar concentration siRNA was ineffective in the liver and jejunum. Cholesterol linked siRNA was only effective in the jejunum (c50% reduction in mRNA) Fig1. Only the LNA mediated inhibition of ApoB expression was paralleled by a drop in serum cholesterol in the host animal. In a second model siRNA molecules targeting Hif-1a mRNA (Yu et al Lab Invest84, 553–561 2004) were compared to our lead LNA molecule targeting Hif-1a, SPC2968. Interestingly in in vitro analyses these 2 molecules were equally effective. However in a murine model the increased half life of the LNA molecules translated to a potent inhibition of Hif-1a as measured by QPCR. This effect was noted in jejunum and liver, and persisted for at least 4 days. Hif-1a inhibition mediated by siRNA was not seen in any tissue analysed (Fig 2). Finally a 3rd molecule targeting Bcl-2 has entered clinical Phase 1 trials, and data will be presented documenting its improved affinity and stabitily in relation to competitor molecules such as Genasense. Figure Figure

Lentivirus-Mediated RNA Interference Targeting the Long Noncoding RNA HOTAIR Inhibits Proliferation and Invasion of Endometrial Carcinoma Cells In Vitro and In Vivo

2014 ◽  
Vol 24 (4) ◽  
pp. 635-642 ◽  
Author(s):  
Jiaming Huang ◽  
Peiqi Ke ◽  
Luyan Guo ◽  
Wei Wang ◽  
Hao Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Proliferation And Invasion

ObjectiveThe overexpression of long noncoding RNA HOTAIR is associated with various aggressive solid carcinomas. However, its relationship with endometrial carcinoma has not been reported. The present study aimed to investigate the expression of the long noncoding RNA HOTAIR in endometrial carcinoma, its relationship with the carcinoma’s clinicopathologic features, and the biological function of HOTAIR in regulating endometrial cancer cell proliferation and invasion in vitro and in vivo.MethodsThe expression of HOTAIR was detected in different tissues and cell lines by real-time PCR. Lentivirus-mediated HOTAIR-specific shRNAvectors were transfected into endometrial cancer HEC-1A cells. Cell proliferation and colony formation were examined by CCK-8 assays and colony formation assays, respectively. Invasion and migration were examined by Transwell assays. Flow cytometry assay was used to examine the cell cycle. In addition, xenograft model assays were performed to analyze the growth of endometrial cancer cells in vivo.ResultsOur data showed that HOTAIR expression was higher in endometrial cancer cells and tissues than in normal endometrial tissues. HOTAIR expression was closely related to the tumor stage (P= 0.045), myometrial invasion (P= 0.014), and lymph node metastasis (P= 0.033). The down-regulation of HOTAIR resulted in a significant inhibition of cell proliferation, migration, and invasion and in cell cycle arrest at the G0/G1 phase. Furthermore, HOTAIR depletion significantly suppressed the endometrial cancer tumorigenesis in vivo.ConclusionsThis study is the first to suggest that HOTAIR plays an important role in the carcinogenesis of endometrial cancer. Targeting HOTAIR may be a novel therapeutic strategy for endometrial cancer.

miR-142 Suppresses Endometrial Cancer Proliferation In Vitro and In Vivo by Targeting Cyclin D1

2019 ◽  
Vol 38 (2) ◽  
pp. 144-150 ◽  
Author(s):  
Yi Su ◽  
Jing Wang ◽  
Zhao Ma ◽  
Wenjing Gong ◽  
Lianzhi Yu
Keyword(s):  
Endometrial Cancer ◽  
Cyclin D1 ◽  
Cancer Proliferation ◽  
Proliferation In Vitro

scholarly journals Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kazuhiro Ikeda ◽  
Kuniko Horie-Inoue ◽  
Takashi Suzuki ◽  
Rutsuko Hobo ◽  
Norie Nakasato ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Tricarboxylic Acid Cycle ◽  
Hypoxia Tolerance ◽  
Breast Cancer Patients ◽  
Cancer Cell Growth

Abstract Recent advance in cancer research sheds light on the contribution of mitochondrial respiration in tumorigenesis, as they efficiently produce ATP and oncogenic metabolites that will facilitate cancer cell growth. Here we show that a stabilizing factor for mitochondrial supercomplex assembly, COX7RP/COX7A2L/SCAF1, is abundantly expressed in clinical breast and endometrial cancers. Moreover, COX7RP overexpression associates with prognosis of breast cancer patients. We demonstrate that COX7RP overexpression in breast and endometrial cancer cells promotes in vitro and in vivo growth, stabilizes mitochondrial supercomplex assembly even in hypoxic states, and increases hypoxia tolerance. Metabolomic analyses reveal that COX7RP overexpression modulates the metabolic profile of cancer cells, particularly the steady-state levels of tricarboxylic acid cycle intermediates. Notably, silencing of each subunit of the 2-oxoglutarate dehydrogenase complex decreases the COX7RP-stimulated cancer cell growth. Our results indicate that COX7RP is a growth-regulatory factor for breast and endometrial cancer cells by regulating metabolic pathways and energy production.

In Vitro and Vivo Activity Against Multiple Myeloma Cells Of a Novel Locked Nucleic Acid (LNA)-Mir-221 Inhibitor

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3166-3166
Author(s):  
Maria Teresa Di Martino ◽  
Annamaria Gullà ◽  
Maria Eugenia Gallo Cantafio ◽  
Emanuela Altomare ◽  
Nicola Amodio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Nucleic Acid ◽  
Luciferase Activity ◽  
Locked Nucleic Acid ◽  
Phase Cell ◽  
Target Sequence ◽  
Systemic Delivery ◽  
Anti Tumor Activity

Abstract miR-221/222 are two highly homologous microRNAs (miRNAs), encoded in tandem on the chromosome X, whose up-regulation has been found in several malignancies and are thought to promote cell proliferation via down-regulation of p27 and/or p57, two negative regulators of G1 to S phase cell cycle progression. We demonstrated up-regulation of both miRNAs in malignant plasma cells (PCs) from multiple myeloma (MM) patients belonging to distinct TC (translocation/Cyclin) groups, including TC2 and TC4. A rising body of evidence suggests that silencing miRNAs with oncogenic potential could represent a novel approach for human cancer therapy. We previously demonstrated that silencing miR-221/222 exerts significant anti-MM activity and triggers canonical targets in vitro and in vivo. Here, in the aim to progress to clinical translation of our proof-of-principle findings, we investigated the anti-tumor activity and the appropriateness for systemic delivery of a novel and originally designed LNA-miR-221, a 13-mer antisense miR-221 inhibitor, which took advantage of locked nucleic acid (LNA) technology and phosphorothioate backbone chemistry for increasing affinity for miR-221 and nuclease resistance. We found that enforced ectopic expression of LNA-miR-221 in t(4;14) MM cells significantly inhibited growth and survival of MM cells in vitro. In treated cells, we detected knock down of miR-221/222 together and increased levels of both p27Kip1 mRNA and protein. Specific activity of this LNA-miR-221 inhibitor was confirmed by the use of a 3’UTR reporter (luciferase renilla/firefly) constructs containing, miR-221 target site. This construct was co-transfected either with miR-221/222 mimics or LNA-miR-221 inhibitor into MM cells. As predicted, a reduced luciferase activity was detected in miR-221/222 mimics co-transfected cells with each 3’UTR reporter plasmid, while increase luciferase activity was measured in MM cells co-transfected LNA-miR-221 inhibitors indicating an efficient and stable binding to the miRNA target sequence. Importantly, we evaluated the systemic delivery of the LNA-miR-221 inhibitor with saline solution vehicle alone by intraperitoneal or intravenous injection route against MM xenografts in SCID/NOD mice. Significant anti-tumor activity was achieved after 2 weeks of treatment at similar extent by both injection routes. Retrieved tumors from treated animals showed efficient inhibition of miR-221/222, as demonstrated by increased levels of p27Kip1 protein in vivo. H&E staining and immunohistochemical analysis showed wide necrosis areas, reduced Ki67 and a significant increase of p27Kip1 cytoplasmic expression in retrieved tumors from LNA-miR-221 inhibitor-treated mice. No changes in mice behavior or organ toxicity were observed in treated mice. Taken together these findings support the rationale for development of this novel and highly efficient LNA-miR-221 inhibitor as a promising anti-MM drug in subsequent primate toxicology studies. Supported by the Italian Association for Cancer Research (AIRC), PI: PT. “Special Program Molecular Clinical Oncology - 5 per mille” n. 9980, 2010/15. Disclosures: No relevant conflicts of interest to declare.

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