Design, Modeling and Computational Analysis of crRNA to Regulate MetastamiR-10b and MetastamiR-126 in Post-transcriptional Level by CRISPR-C2c2 (Cas13a) Technique

Introduction: Metastasis is one the most important causes of mortality in cancer patients. Recent studies have shown the metastatic potential of a specific group of microRNAs called metastamirs.  miR-126 is shown to be correlated with the colorectal liver metastasis. Also, overexpression of miR-10b...

Full description

Bibliographic Details
Main Authors: Fatemeh Ebrahimi Tarki, Mahsa Bourbour, Mahboobe Zarrabi
Format: Article
Language:fas
Published: Kerman University of Medical Sciences 2020-03-01
Series:مجله انفورماتیک سلامت و زیست پزشکی
Subjects:
Online Access:http://jhbmi.ir/article-1-390-en.html
_version_ 1811176307430522880
author Fatemeh Ebrahimi Tarki
Mahsa Bourbour
Mahboobe Zarrabi
author_facet Fatemeh Ebrahimi Tarki
Mahsa Bourbour
Mahboobe Zarrabi
author_sort Fatemeh Ebrahimi Tarki
collection DOAJ
description Introduction: Metastasis is one the most important causes of mortality in cancer patients. Recent studies have shown the metastatic potential of a specific group of microRNAs called metastamirs.  miR-126 is shown to be correlated with the colorectal liver metastasis. Also, overexpression of miR-10b has been reported in metastatic breast cancer.  Therefore, down regulation of these miRNAs at transcriptional level can reduce the probability of metastasis. This study analyzes targeting of miRNAs precursors using CRISPR-C2c2 (Cas13a) technique. Method: To conduct this study, we used bioinformatics and structural bioinformatics methods. The structure of C2c2 (Cas13a) enzyme was obtained from RCSB database, and the sequences of miRNAs and their precursors were collected from MirBase and Mirnamap. The crRNAs were designed, evaluated and checked for their specificity by using CRISPR-RT. The modeling of the three-dimensional structure of the designed crRNAs was performed by RNAbuilder 2.8.2 software. We used Hdock server to perform molecular docking to assess the energy level and the position of docked molecules.  Result: The crRNA designed for mir-126 showed high structural similarity with the situation observed in nature and appropriate orientation was obtained. In the case of crRNA designed to target mir-10b, despite high specificity, the correct orientation was not established. Conclusion: Sequence-based evaluation of crRNAs designed for RNA-level editing is insufficient, and it is recommended that, along with specificity, simulation and molecular docking studies, be performed for higher accuracy.
first_indexed 2024-04-10T19:49:35Z
format Article
id doaj.art-7d51f099f84248d7a12a35dacf3cd822
institution Directory Open Access Journal
issn 2423-3870
2423-3498
language fas
last_indexed 2024-04-10T19:49:35Z
publishDate 2020-03-01
publisher Kerman University of Medical Sciences
record_format Article
series مجله انفورماتیک سلامت و زیست پزشکی
spelling doaj.art-7d51f099f84248d7a12a35dacf3cd8222023-01-28T10:30:48ZfasKerman University of Medical Sciencesمجله انفورماتیک سلامت و زیست پزشکی2423-38702423-34982020-03-0164320332Design, Modeling and Computational Analysis of crRNA to Regulate MetastamiR-10b and MetastamiR-126 in Post-transcriptional Level by CRISPR-C2c2 (Cas13a) TechniqueFatemeh Ebrahimi Tarki0Mahsa Bourbour1Mahboobe Zarrabi2 M.Sc. of Microbial Biotechnology, Computational Biology Lab, Biotechnology Dept., Alzahra University, Tehran, Iran M.Sc. of Microbial Biotechnology, Computational Biology Lab, Biotechnology Dept., Alzahra University, Tehran, Iran Ph.D. in Biophysics, Assistant Professor, Computational Biology Lab, Department of Biotechnology Dept., Alzahra University, Tehran, Iran Introduction: Metastasis is one the most important causes of mortality in cancer patients. Recent studies have shown the metastatic potential of a specific group of microRNAs called metastamirs.  miR-126 is shown to be correlated with the colorectal liver metastasis. Also, overexpression of miR-10b has been reported in metastatic breast cancer.  Therefore, down regulation of these miRNAs at transcriptional level can reduce the probability of metastasis. This study analyzes targeting of miRNAs precursors using CRISPR-C2c2 (Cas13a) technique. Method: To conduct this study, we used bioinformatics and structural bioinformatics methods. The structure of C2c2 (Cas13a) enzyme was obtained from RCSB database, and the sequences of miRNAs and their precursors were collected from MirBase and Mirnamap. The crRNAs were designed, evaluated and checked for their specificity by using CRISPR-RT. The modeling of the three-dimensional structure of the designed crRNAs was performed by RNAbuilder 2.8.2 software. We used Hdock server to perform molecular docking to assess the energy level and the position of docked molecules.  Result: The crRNA designed for mir-126 showed high structural similarity with the situation observed in nature and appropriate orientation was obtained. In the case of crRNA designed to target mir-10b, despite high specificity, the correct orientation was not established. Conclusion: Sequence-based evaluation of crRNAs designed for RNA-level editing is insufficient, and it is recommended that, along with specificity, simulation and molecular docking studies, be performed for higher accuracy.http://jhbmi.ir/article-1-390-en.htmlmetastamircripsr-c2c2(cas13a)metastasis inhibitioncrispr-rtcrrna
spellingShingle Fatemeh Ebrahimi Tarki
Mahsa Bourbour
Mahboobe Zarrabi
Design, Modeling and Computational Analysis of crRNA to Regulate MetastamiR-10b and MetastamiR-126 in Post-transcriptional Level by CRISPR-C2c2 (Cas13a) Technique
مجله انفورماتیک سلامت و زیست پزشکی
metastamir
cripsr-c2c2(cas13a)
metastasis inhibition
crispr-rt
crrna
title Design, Modeling and Computational Analysis of crRNA to Regulate MetastamiR-10b and MetastamiR-126 in Post-transcriptional Level by CRISPR-C2c2 (Cas13a) Technique
title_full Design, Modeling and Computational Analysis of crRNA to Regulate MetastamiR-10b and MetastamiR-126 in Post-transcriptional Level by CRISPR-C2c2 (Cas13a) Technique
title_fullStr Design, Modeling and Computational Analysis of crRNA to Regulate MetastamiR-10b and MetastamiR-126 in Post-transcriptional Level by CRISPR-C2c2 (Cas13a) Technique
title_full_unstemmed Design, Modeling and Computational Analysis of crRNA to Regulate MetastamiR-10b and MetastamiR-126 in Post-transcriptional Level by CRISPR-C2c2 (Cas13a) Technique
title_short Design, Modeling and Computational Analysis of crRNA to Regulate MetastamiR-10b and MetastamiR-126 in Post-transcriptional Level by CRISPR-C2c2 (Cas13a) Technique
title_sort design modeling and computational analysis of crrna to regulate metastamir 10b and metastamir 126 in post transcriptional level by crispr c2c2 cas13a technique
topic metastamir
cripsr-c2c2(cas13a)
metastasis inhibition
crispr-rt
crrna
url http://jhbmi.ir/article-1-390-en.html
work_keys_str_mv AT fatemehebrahimitarki designmodelingandcomputationalanalysisofcrrnatoregulatemetastamir10bandmetastamir126inposttranscriptionallevelbycrisprc2c2cas13atechnique
AT mahsabourbour designmodelingandcomputationalanalysisofcrrnatoregulatemetastamir10bandmetastamir126inposttranscriptionallevelbycrisprc2c2cas13atechnique
AT mahboobezarrabi designmodelingandcomputationalanalysisofcrrnatoregulatemetastamir10bandmetastamir126inposttranscriptionallevelbycrisprc2c2cas13atechnique