Methodological obstacles in knocking down small noncoding RNAs

Ploner, Andreas; Ploner, Christian; Lukasser, Melanie; Niederegger, Harald; Hüttenhofer, Alexander

doi:10.1261/rna.1740009

Cited by 30 publications

(21 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5A). In contrast, siRNA-mediated silencing of BC040587 was not effective (data not shown), consistent with reports of reduced susceptibility of ncRNAs to siRNA (39).…”

Section: Resultssupporting

confidence: 91%

Recurrent Focal Copy-Number Changes and Loss of Heterozygosity Implicate Two Noncoding RNAs and One Tumor Suppressor Gene at Chromosome 3q13.31 in Osteosarcoma

et al. 2010

View full text Add to dashboard Cite

Osteosarcomas are copy number alteration (CNA)-rich malignant bone tumors. Using microarrays, fluorescence in situ hybridization, and quantitative PCR, we characterize a focal region of chr3q13.31 (osteo3q13.31) harboring CNAs in 80% of osteosarcomas. As such, osteo3q13.31 is the most altered region in osteosarcoma and contests the view that CNAs in osteosarcoma are nonrecurrent. Most (67%) osteo3q13.31 CNAs are deletions, with 75% of these monoallelic and frequently accompanied by loss of heterozygosity (LOH) in flanking DNA. Notably, these CNAs often involve the noncoding RNAs LOC285194 and BC040587 and, in some cases, a tumor suppressor gene that encodes the limbic system-associated membrane protein (LSAMP). Ubiquitous changes occur in these genes in osteosarcoma, usually involving loss of expression. Underscoring their functional significance, expression of these genes is correlated with the presence of osteo3q13.31 CNAs. Focal osteo3q13.31 CNAs and LOH are also common in cell lines from other cancers, identifying osteo3q13.31 as a generalized candidate region for tumor suppressor genes. Osteo3q13.31 genes may function as a unit, given significant correlation in their expression despite the great genetic distances between them. In support of this notion, depleting either LSAMP or LOC285194 promoted proliferation of normal osteoblasts by regulation of apoptotic and cell-cycle transcripts and also VEGF receptor 1. Moreover, genetic deletions of LOC285194 or BC040587 were also associated with poor survival of osteosarcoma patients. Our findings identify osteo3q13.31 as a novel region of cooperatively acting tumor suppressor genes. Cancer Res; 70(1); 160-71. ©2010 AACR.

show abstract

“…5A). In contrast, siRNA-mediated silencing of BC040587 was not effective (data not shown), consistent with reports of reduced susceptibility of ncRNAs to siRNA (39).…”

Section: Resultssupporting

confidence: 91%

Recurrent Focal Copy-Number Changes and Loss of Heterozygosity Implicate Two Noncoding RNAs and One Tumor Suppressor Gene at Chromosome 3q13.31 in Osteosarcoma

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The rapid pace of studies on miR regulation and function necessitates the development of suitable techniques for modulating miRs (133). In addition to these chemically engineered oligonucleotides, locked nucleic acids have been used in vivo to inactivate their function (134,136,137). These are chemically engineered small synthetic RNA molecules that are perfectly complementary to the specific miR target with mispairing at the cleavage site of argonaute 2 (Ago2) or some sort of base modification to inhibit Ago2 cleavage.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis

2011

View full text Add to dashboard Cite

A primary event in atherogenesis is the infiltration of activated inflammatory cells into the arterial wall. There they secrete reactive oxygen species and oxidize lipoproteins, inducing foam cell formation and endothelial cell apoptosis, which in turn lead to plaque growth, erosion, and rupture. In addition, there is evidence that this vicious circle between oxidative stress and inflammation occurs not only in the diseased arterial wall but also in adipose tissues in obesity. In this condition, oxidative stress and inflammation impair adipocyte maturation, resulting in defective insulin action and adipocytokine signaling. This observation raises questions regarding what molecules are probably common regulators of these pathogenic processes in adipose and vascular tissues. Candidates are small, noncoding, microRNAs (miRs) that control gene expression by inducing mRNA degradation or blocking translation. This review summarizes recent insights into the roles of miRs in regulation of oxidative stress and inflammation in vascular and adipose tissues. It emphasizes the role of miR-containing microvesicles in the interaction between inflammatory cells and endothelial cells within these tissues and in communication between these tissues, possibly explaining the similarity and the simultaneity of molecular changes and interactions in adipose and vascular tissues.

show abstract

“…More research to identify miRNA markers for breast, lung, ovarian, cervical cancer and leukaemia is ongoing and may lead to a more refined cancer diagnostics marker in the future. Further application of miRNA as gene therapies to deliver tumor suppression as miRNA, anti-miRNA oligonucleotides (AMOs), or cholesterol conjugated AMOs, so-called antagomirs, are also in progress (125-127). It has been documented that miR 146, 181, 155 play an important role in immune regulation and inflammation.…”

Section: Monocytes Are Innate Immune Effectors and Sensitive Sensors mentioning

confidence: 99%

Cancer and Inflammation: Promise for Biologic Therapy

Demaria

Pikarsky

Karin

et al. 2010

Journal of Immunotherapy

291

190

View full text Add to dashboard Cite

Cancers often arise as the end stage of inflammation in adults, but not in children. As such there is a complex interplay between host immune cells during neoplastic development, with both an ability to promote cancer as well as limit or eliminate it, most often complicit with the host. In humans, defining inflammation and the presence of inflammatory cells within or surrounding the tumor is a critical aspect of modern pathology. Groups defining staging for neoplasms are strongly encouraged to assess and incorporate measures of the presence of apoptosis, autophagy, and necrosis as well as the nature and quality of the immune infiltrate. Both environmental as well as genetic factors enhance the risk of cigarette smoking, H. pylori, hepatitis B/C, human papilloma virus, solar irradiation, asbestos, pancreatitis, or other causes of chronic inflammation. Identifying suitable genetic polymorphisms in cytokines, cytokine receptors, and Toll-like receptors among other immune response genes is also seen as high value as genomic sequencing becomes less expensive. Animal models which incorporate and assess not only the genetic anlagen but also the inflammatory cells and the presence of microbial pathogen [PAMPs] and damage associated molecular pattern molecules [DAMPs] are necessary. Identifying micro-RNAs involved in regulating the response to damage or injury are seen as highly promising. Although no therapeutic strategies to prevent or treat cancers based on insights into inflammatory pathways are currently approved for the common epithelial malignancies, there remains substantial interest in agents targeting COX2 or PPARγ, ethyl pyruvate, as well as steroids and several novel agents on the horizon.

show abstract

Methodological obstacles in knocking down small noncoding RNAs

Cited by 30 publications

References 44 publications

Recurrent Focal Copy-Number Changes and Loss of Heterozygosity Implicate Two Noncoding RNAs and One Tumor Suppressor Gene at Chromosome 3q13.31 in Osteosarcoma

Recurrent Focal Copy-Number Changes and Loss of Heterozygosity Implicate Two Noncoding RNAs and One Tumor Suppressor Gene at Chromosome 3q13.31 in Osteosarcoma

MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis

Cancer and Inflammation: Promise for Biologic Therapy

Contact Info

Product

Resources

About