RNA Interference in Functional Genomics and Medicine

Kim, V. Narry

doi:10.3346/jkms.2003.18.3.309

Cited by 50 publications

(31 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…RNA interference is described as a response to double-stranded RNA that leads to sequencespecific posttranscriptional gene silencing [24]. In regard to siRNA, it is incorporated into a nuclease complex called the RNA-induced silencing complex (RISC) that targets and cleaves mRNA complementary to the siRNA and thus lowers its expression [25]. Therefore, it is assumed that, when induced by HAS-2-siRNA, the RISC-mediated cleavage of HAS-2-RNA results in the degradation of mRNA and leads to a decrease in mRNA expression, which further causes a decrease in HAS-2 expression due to the lack of its corresponding mRNA.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Effects of HAS-2 Gene Silencing on the Proliferation and Apoptosis of the MCF-7 Human Breast Cancer Cell Line

Zhang¹,

Feng²,

Wang³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. This study is aimed to investigate the effects of silencing the HAS-2 gene on the proliferation and apoptosis of human breast cancer cells. Methods: MCF-7 cells were collected and assigned into control, scrambled siRNA and HAS-2- siRNA groups. After transfection, the morphological changes in the MCF-7 cells were observed using phase contrast microscopy. qRT-PCR and Western blot assays were used to detect the mRNA and protein expression of apoptosis-related proteins. CCK-8 and flow cytometry were performed to evaluate cell proliferation, the cell cycle and apoptosis. Results: In the control and the scrambled siRNA groups, cells grew adhered to the wall and mainly showed a spindle shape with a clear nucleolus. Compared with the control and scrambled siRNA groups, increases in the number of cells in early apoptosis and metaphase cells in apoptosis were observed in the HAS-2-siRNA group. The HAS-2-siRNA group showed decreased expression of HAS-2 relative to that in the control and scrambled siRNA groups. No significant differences in cell proliferation, cell cycle distribution or apoptosis were noted between the control and scrambled siRNA groups. In the HAS-2-siRNA group, the cell proliferation ability decreased significantly, but the number of cells in the G0/G1 stage, the number of apoptotic cells and the expression of caspase-3 and caspase-9 increased significantly. Conclusion: Our findings indicate that HAS-2 gene silencing may inhibit proliferation and promote apoptosis in the MCF-7 human breast cancer cell line.

show abstract

Section: Discussionmentioning

confidence: 99%

In Vitro Effects of HAS-2 Gene Silencing on the Proliferation and Apoptosis of the MCF-7 Human Breast Cancer Cell Line

Zhang¹,

Feng²,

Wang³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Even if several ErbB2 cDNAs were used for overexpression, it would be difficult to mimic the effects of a single ATF. Similarly, when inhibiting gene expression by using RNA interference, multiple regions of the mRNA are generally targeted by using multiple siRNAs to ensure successful target down-regulation; this increases the potential for undesirable off-target effects (13,39). Zinc finger TFs allow either upregulation of all splice variants or efficient down-regulation through targeting of a single sequence.…”

Section: Discussionmentioning

confidence: 99%

Zinc Finger Transcription Factors Designed for Bispecific Coregulation of ErbB2 and ErbB3 Receptors: Insights into ErbB Receptor Biology

Lund

Popkov

Magnenat

et al. 2005

Molecular and Cellular Biology

View full text Add to dashboard Cite

Signaling through the ErbB family of tyrosine kinase receptors in normal and cancer-derived cell lines contributes to cell growth and differentiation. In this work, we altered the levels of ErbB2 and ErbB3 receptors, individually and in combination, by using 6-finger and 12-finger synthetic zinc finger protein artificial transcription factors (ATFs) in an epidermoid squamous cell carcinoma line, A431. We successfully designed 12-finger ATFs capable of coregulating ErbB3 and ICAM-1 or ErbB2 and ErbB3. With ATFs, the effects of changes in ErbB2 and ErbB3 receptor levels were evaluated by using cell proliferation, cell migration, and cell signaling assays. Cell proliferation was increased when ErbB2 and ErbB3 were both overexpressed. Cell migration on collagen was decreased when ErbB2 was down-regulated, yet migration on laminin was significantly increased with ErbB3 overexpression. ErbB2 and ErbB3 overexpression also stimulated the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. Our ATF approach has elucidated differences in ErbB receptor-mediated proliferation, migration, and intracellular signaling that cannot be explained merely by the presence or absence of particular ErbB receptors and emphasizes the dynamic nature of the ErbB signaling system. The transcription factor approach developed here provides a gene-economical route to the regulation of multiple genes and may be important for complex gene therapies.Signaling from ErbB tyrosine kinase receptors influences diverse aspects of a cell's biology that include growth, differentiation, migration, and apoptosis (29, 84). ErbB1 (EGFR/ HER1) was the first member of the family identified. Based on homology to ErbB1, three additional family members, ErbB2 (HER2/p185), ErbB3 (HER3), and ErbB4 (HER4), were identified (41,56,60,77). In normal development, binding of a growth factor ligand induces dimerization of ErbB receptors. Subsequently, the cytoplasmic tails are transphosphorylated. Each ErbB receptor has a unique pattern of phosphorylation sites that recruit various secondary signaling proteins (23,51,52,55,71). Ongoing research shows that the identity of the ligand bound, the amount of ligand, and the identities of dimers formed determine the activation of a particular intracellular signaling pathway such as the mitogen-activated protein kinase (MAPK), the stress-activated protein kinase, the protein kinase C, or the Akt pathway (53,61,72). The combination of at least 10 different ligands and 10 possible receptor dimers of the ErbB system form a signaling network essential for development (15,34).Various cancers, including those of the breast, head and neck, kidney, prostate, colon, pancreas, bladder, lung, and ovaries, are associated with overexpression of ErbB receptors (11,59,84). Research using breast cancer models has identified a dominant role for ErbB2 in tumor cell proliferation and metastasis (35,64,73,74). ErbB2 is the preferred dimerization partner for all ErbB receptors, and dimers containing ErbB2 have higher ligand af...

show abstract

“…siRNA as a therapeutic molecule is very effective at knocking down molecular pathways that are pathogenic 15 . However, its application in the clinic is often limited by its susceptibility to enzymatic degradation in blood, non-specific uptake by cells, and the difficulty involved in the transfection of siRNA to cells because of its relatively large size and polarity 16, 17…”

Section: Introductionmentioning

confidence: 99%

siRNA-Encapsulated Hybrid Nanoparticles Target Mutant K-ras and Inhibit Metastatic Tumor Burden in a Mouse Model of Lung Cancer

Perepelyuk

Shoyele

Birbe

et al. 2017

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

There is an unmet need in the development of an effective therapy for mutant K-ras-expressing non-small-cell lung cancer (NSCLC). Although various small molecules have been evaluated, an effective therapy remains a dream. siRNAs have the potential to downregulate mutant K-ras both at the protein and mRNA levels. However, a safe and effective delivery of siRNAs to tumors remains a limitation to their translational application in the treatment of this highly debilitating disease. Here we developed a novel hybrid nanoparticle carrier for effective delivery of anti-mutant K-ras to NSCLC (AKSLHN). The ability of this treatment modality to regress lung tumors in mouse models was evaluated as a monotherapy or as a combination treatment with erlotinib. Further, the toxicity of this treatment modality to healthy tissues was evaluated, along with its ability to elicit immune/inflammatory reactions. The results suggest that this treatment modality is a promising prospect for the treatment of mutant K-ras-expressing NSCLC without any accompanying toxicity. However, further understanding of the cellular-level interaction between AHSLHN and erlotinib needs to be attained before this promising treatment modality can be brought to the bedside.

show abstract

RNA Interference in Functional Genomics and Medicine

Cited by 50 publications

References 98 publications

In Vitro Effects of HAS-2 Gene Silencing on the Proliferation and Apoptosis of the MCF-7 Human Breast Cancer Cell Line

In Vitro Effects of HAS-2 Gene Silencing on the Proliferation and Apoptosis of the MCF-7 Human Breast Cancer Cell Line

Zinc Finger Transcription Factors Designed for Bispecific Coregulation of ErbB2 and ErbB3 Receptors: Insights into ErbB Receptor Biology

siRNA-Encapsulated Hybrid Nanoparticles Target Mutant K-ras and Inhibit Metastatic Tumor Burden in a Mouse Model of Lung Cancer

Contact Info

Product

Resources

About