Difference between revisions of "Team:Ain Shams-Egypt/Description"

Line 31: Line 31:
 
</div>
 
</div>
 
<div class = "description">
 
<div class = "description">
<p>We are using mammalian cells to see the expression of the circular RNA in the deregulated micro RNA environment of the cancer cells in tissue cultures, prove their role and detect if they can serve as a biomarker in HCC, Detect the relation between its expression levels and rate of progression and the possibility of using it as a potential novel target for the treatment of HCC.
+
<p> Hepatocellular carcinoma (HCC) is one of the most common malignancies and one of the leading causes of cancer-related death globally .Circular RNAs (circRNAs) are a large class of RNAs that, unlike linear RNAs, form covalently closed continuous loops and have recently shown huge capabilities as gene regulators in mammals [1] .  
</p>
+
+
</div>
+
</div>
+
</div>
+
 
+
<p class="text-gray"><b>Introduction/Background: </b> Hepatocellular carcinoma (HCC) is one of the most common malignancies and one of the leading causes of cancer-related death globally .Circular RNAs (circRNAs) are a large class of RNAs that, unlike linear RNAs, form covalently closed continuous loops and have recently shown huge capabilities as gene regulators in mammals [1] .  
+
 
</p>
 
</p>
 
<p> Interestingly, they are found to be enormously abundant, evolutionally conserved and relatively stable in cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as microRNA (miRNA) sponges, binding to RNA-associated proteins to form RNA-protein complexes and then regulating gene transcription. Importantly, circRNAs associate with cancer-related miRNAs and the circRNA-miRNA axes are involved in cancer-related pathways. Some synthetic circRNAs have shown remarkable anti-cancer effects [2] . The current methods to detect and characterize circRNAs are still limited and challenge-able [3 ]. The emerging roles of the highly complex network of circRNAs, which communicate via miRNA and the overwhelming number of identified circRNA structures leads to exciting new avenues of research to uncover the full biologic functions of these n cRNAs in cellular regulation and human disease. The clinical trial treating some human diseases with synthetic miRNA inhibitors is already in phase 2a [4 ]. Like these small RNA-based drugs (e.g. miRNAs), such circRNA molecules face multiple delivery challenges such as lack of targeted delivery in cancer targeted therapy [5 ].  
 
<p> Interestingly, they are found to be enormously abundant, evolutionally conserved and relatively stable in cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as microRNA (miRNA) sponges, binding to RNA-associated proteins to form RNA-protein complexes and then regulating gene transcription. Importantly, circRNAs associate with cancer-related miRNAs and the circRNA-miRNA axes are involved in cancer-related pathways. Some synthetic circRNAs have shown remarkable anti-cancer effects [2] . The current methods to detect and characterize circRNAs are still limited and challenge-able [3 ]. The emerging roles of the highly complex network of circRNAs, which communicate via miRNA and the overwhelming number of identified circRNA structures leads to exciting new avenues of research to uncover the full biologic functions of these n cRNAs in cellular regulation and human disease. The clinical trial treating some human diseases with synthetic miRNA inhibitors is already in phase 2a [4 ]. Like these small RNA-based drugs (e.g. miRNAs), such circRNA molecules face multiple delivery challenges such as lack of targeted delivery in cancer targeted therapy [5 ].  
 
</p>  
 
</p>  
  
<p>Recently, researchers used circular sponge activity help in countering harmful miRNAactivity.The circularized miRNA sponges displayed superior anti-cancer activities compared to the linear sponges in malignant melanoma cell lines [6] . As an alternative to the use of the vectors expressing linear sponges, the use of the expression vector for RNA circles opens new way to deliver miRNA sponges with persistent effects. The availability of circularizing the miRNA sponge in cells is a candidate for a new methodology for RNA-based cancer therapy [7] . </p>  
+
<p>Recently, researchers used circular sponge activity help in countering harmful miRNA activity.The circularized miRNA sponges displayed superior anti-cancer activities compared to the linear sponges in malignant melanoma cell lines [6] . As an alternative to the use of the vectors expressing linear sponges, the use of the expression vector for RNA circles opens new way to deliver miRNA sponges with persistent effects. The availability of circularizing the miRNA sponge in cells is a candidate for a new methodology for RNA-based cancer therapy [7] . </p>  
  
 
<p>Since certain circRNA has many binding sites for a specific miRNA, it is more effective than typical miRNA inhibitors . With the new discovery of miRNA management by naturally occurring circRNAs, RNA circles may prove to be well-suited decoy-type miRNA inhibitors serving as new generation of miRNA inhibitors[8]. Such synthetic circRNA inhibitors might be future targets for therapies and soon appear as new therapeutic strategies in cancers. </p>  
 
<p>Since certain circRNA has many binding sites for a specific miRNA, it is more effective than typical miRNA inhibitors . With the new discovery of miRNA management by naturally occurring circRNAs, RNA circles may prove to be well-suited decoy-type miRNA inhibitors serving as new generation of miRNA inhibitors[8]. Such synthetic circRNA inhibitors might be future targets for therapies and soon appear as new therapeutic strategies in cancers. </p>  
Line 49: Line 42:
 
<p> For this project, we will use a variety of computational algorithms for the prediction of a set of a cirRNA and a selected competing endogenous RNA involved in HCC development .Finally, we will establish functional hypothesis for the cirRNA network in HCC using public microarray public database to identify molecular signatures  associated with HCC . We will adopt a novel strategy for miRNA suppression by using circRNAs. These findings may provide the rationale for designing novel therapeutic approaches using artificial synthetic circuit modulating dysregulated circular RNA network. </p>  
 
<p> For this project, we will use a variety of computational algorithms for the prediction of a set of a cirRNA and a selected competing endogenous RNA involved in HCC development .Finally, we will establish functional hypothesis for the cirRNA network in HCC using public microarray public database to identify molecular signatures  associated with HCC . We will adopt a novel strategy for miRNA suppression by using circRNAs. These findings may provide the rationale for designing novel therapeutic approaches using artificial synthetic circuit modulating dysregulated circular RNA network. </p>  
  
 +
</p>
 +
 +
</div>
 +
</div>
 +
</div>
  
 
+
 
+
  
  

Revision as of 19:23, 19 October 2016

WATTS-APTAMER - UP_PRETORIA iGEM

WATTS-APTAMER - UP_PRETORIA iGEM

Project Description

Abstract: Treatment options for HCC are limited and often inefficient. Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. So as a team that believes in synthetic biology we searched how could we help our community regarding this problem & we found that it’s been shown that circular RNA (circ.RNA) is associated with human cancers, & some studies have been reported in HCC. Circular RNA will be delivered as it is a new area of research with around 130 circular RNA sequence detected in HCC only less than 10% of these has been investigated and characterized through previous studies. Circular RNA is a type of RNA which, that forms a covalently closed continuous loop. This feature confers numerous properties to circular RNAs, many of which have only recently been identified. Circular RNAs have recently shown potential as gene regulators. Like many other alternative noncoding isoforms, the biological function of most circular RNAs are unclear, circular RNAs do not have 5' or 3' ends so they are resistant to exonuclease-mediated degradation and more stable than most linear RNAs in cells.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and one of the leading causes of cancer-related death globally .Circular RNAs (circRNAs) are a large class of RNAs that, unlike linear RNAs, form covalently closed continuous loops and have recently shown huge capabilities as gene regulators in mammals [1] .

Interestingly, they are found to be enormously abundant, evolutionally conserved and relatively stable in cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as microRNA (miRNA) sponges, binding to RNA-associated proteins to form RNA-protein complexes and then regulating gene transcription. Importantly, circRNAs associate with cancer-related miRNAs and the circRNA-miRNA axes are involved in cancer-related pathways. Some synthetic circRNAs have shown remarkable anti-cancer effects [2] . The current methods to detect and characterize circRNAs are still limited and challenge-able [3 ]. The emerging roles of the highly complex network of circRNAs, which communicate via miRNA and the overwhelming number of identified circRNA structures leads to exciting new avenues of research to uncover the full biologic functions of these n cRNAs in cellular regulation and human disease. The clinical trial treating some human diseases with synthetic miRNA inhibitors is already in phase 2a [4 ]. Like these small RNA-based drugs (e.g. miRNAs), such circRNA molecules face multiple delivery challenges such as lack of targeted delivery in cancer targeted therapy [5 ].

Recently, researchers used circular sponge activity help in countering harmful miRNA activity.The circularized miRNA sponges displayed superior anti-cancer activities compared to the linear sponges in malignant melanoma cell lines [6] . As an alternative to the use of the vectors expressing linear sponges, the use of the expression vector for RNA circles opens new way to deliver miRNA sponges with persistent effects. The availability of circularizing the miRNA sponge in cells is a candidate for a new methodology for RNA-based cancer therapy [7] .

Since certain circRNA has many binding sites for a specific miRNA, it is more effective than typical miRNA inhibitors . With the new discovery of miRNA management by naturally occurring circRNAs, RNA circles may prove to be well-suited decoy-type miRNA inhibitors serving as new generation of miRNA inhibitors[8]. Such synthetic circRNA inhibitors might be future targets for therapies and soon appear as new therapeutic strategies in cancers.

For this project, we will use a variety of computational algorithms for the prediction of a set of a cirRNA and a selected competing endogenous RNA involved in HCC development .Finally, we will establish functional hypothesis for the cirRNA network in HCC using public microarray public database to identify molecular signatures associated with HCC . We will adopt a novel strategy for miRNA suppression by using circRNAs. These findings may provide the rationale for designing novel therapeutic approaches using artificial synthetic circuit modulating dysregulated circular RNA network.

GOAL: To evaluate the therapeutic efficacy of Circular RNA-miRNA based synthetic circuit in hepatocellular carcinoma cell line.

WATTS-APTAMER - PRETORIA_UP iGEM