Targeting Positive Regulators of Sonic Hedgehog Signaling Pathway in Medulloblastoma by Designing CRISPR/Cas۹ Single Guide RNAs

  • سال انتشار: 1402
  • محل انتشار: مجله علمی پژوهشی دانشگاه علوم پزشکی زنجان، دوره: 31، شماره: 149
  • کد COI اختصاصی: JR_ZUMS-31-149_010
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 35
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نویسندگان

Mehrdad Ghorbanlou

Dept. of Anatomy, School of medicine, Iran University of Medical Sciences, Tehran, Iran

Hasan Marzban

Children’s Hospital Research Institute of Manitoba (CHRIM), College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

Mehdi Mehdizadeh

Reproductive Sciences and Technology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

چکیده

Background and Objective: Medulloblastoma formation is importantly related to granular cell proliferation and differentiation, processes which are under the influence of sonic hedgehog (SHH) signaling. Exons of genes encoding different components of this signaling pathway (e.g., ligands, co-receptor, transcription factors, and target genes) were investigated to identify the proper single guide RNAs for selective targeting of positive regulators of the SHH pathway. Materials and Methods: The genomic DNA sequences of corresponding genes of several positive regulators of the SHH pathway (in Homo Sapiens), including SHH, SMO, GLI۱, GLI۲, MYCN, and MYC, were retrieved from the National Center for Biotechnology Information (NCBI) gene database. Next, the exon sequences of these genes were identified using protospacer adjacent motif (PAM) of NGG and Streptococcus pyogenes Cas۹ nuclease and evaluated by CRISPOR software to select the best sgRNA for each target gene. Results: The analyses revealed the best sgRNAs for the SHH, SMO, GLI۱, GLI۲, MYCN, and MYC genes targeted exon ۱, -۴, -۴, -۵, -۲ and -۲, respectively. Proper sgRNAs for targeting each exon in each gene were also identified. Conclusion: This study revealed possible specific exonic targets of components of the SHH signaling pathway through designing proper sgRNAs using the CRISPR/Cas۹ genome editing approach.

کلیدواژه ها

CRISPR/Cas۹, Sonic Hedgehog, Medulloblastoma, Guide RNA, Genome

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