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Circular rnas in hedgehog signaling activation and hedgehog‐mediated medulloblastoma tumors

Azatyan, Ani ; Zhang, Shasha ; Darabi, Anna LU ; Siesjö, Peter LU orcid ; Wang, Ting and Zaphiropoulos, Peter G. (2021) In Cancers 13(20).
Abstract

Within the past decade, circular RNAs have largely emerged as novel regulators of human biology, including brain function and cancer development. On the other hand, the Hedgehog pathway has established roles in regulating biological processes, including tumorigenesis. Here, the circular RNA transcriptome, in the context of Hedgehog signaling activation of medulloblastoma Daoy and human embryonic palatal mesenchyme HEPM cells, was determined. In total, 29 out of the 30 selected circular RNAs were validated by Sanger sequencing, with some regulated to a lim-ited extent by Hedgehog signaling. Interestingly, back‐spliced junctions, the marker of exonic RNA circles, were also identified at a low frequency within poly (A) mRNAs, reflecting... (More)

Within the past decade, circular RNAs have largely emerged as novel regulators of human biology, including brain function and cancer development. On the other hand, the Hedgehog pathway has established roles in regulating biological processes, including tumorigenesis. Here, the circular RNA transcriptome, in the context of Hedgehog signaling activation of medulloblastoma Daoy and human embryonic palatal mesenchyme HEPM cells, was determined. In total, 29 out of the 30 selected circular RNAs were validated by Sanger sequencing, with some regulated to a lim-ited extent by Hedgehog signaling. Interestingly, back‐spliced junctions, the marker of exonic RNA circles, were also identified at a low frequency within poly (A) mRNAs, reflecting exon repetition events. Thirteen circular RNAs had reduced expression in human medulloblastoma tumors in comparison to normal cerebellum. For seven out of these thirteen RNA circles, the linear mRNAs origi-nating from the same genes did not exhibit a reduced expression. Depletion and/or overexpression of these seven circular RNAs minimally affected medulloblastoma cell proliferation. These findings highlight that differential expression of a gene product may not necessarily elicit an obvious phenotypic impact. Consequently, further analysis is required to determine the possible subtle contri-butions to the development of this cerebellar tumor.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Back‐spliced junction, Cerebellar tumor, CircRNA, Hedgehog pathway, RNA‐seq
in
Cancers
volume
13
issue
20
article number
5138
publisher
MDPI AG
external identifiers
  • scopus:85116975531
  • pmid:34680287
ISSN
2072-6694
DOI
10.3390/cancers13205138
language
English
LU publication?
yes
id
ed838023-3e40-40be-9fff-e0eecaa577a0
date added to LUP
2021-11-01 14:57:31
date last changed
2024-06-15 19:35:05
@article{ed838023-3e40-40be-9fff-e0eecaa577a0,
  abstract     = {{<p>Within the past decade, circular RNAs have largely emerged as novel regulators of human biology, including brain function and cancer development. On the other hand, the Hedgehog pathway has established roles in regulating biological processes, including tumorigenesis. Here, the circular RNA transcriptome, in the context of Hedgehog signaling activation of medulloblastoma Daoy and human embryonic palatal mesenchyme HEPM cells, was determined. In total, 29 out of the 30 selected circular RNAs were validated by Sanger sequencing, with some regulated to a lim-ited extent by Hedgehog signaling. Interestingly, back‐spliced junctions, the marker of exonic RNA circles, were also identified at a low frequency within poly (A) mRNAs, reflecting exon repetition events. Thirteen circular RNAs had reduced expression in human medulloblastoma tumors in comparison to normal cerebellum. For seven out of these thirteen RNA circles, the linear mRNAs origi-nating from the same genes did not exhibit a reduced expression. Depletion and/or overexpression of these seven circular RNAs minimally affected medulloblastoma cell proliferation. These findings highlight that differential expression of a gene product may not necessarily elicit an obvious phenotypic impact. Consequently, further analysis is required to determine the possible subtle contri-butions to the development of this cerebellar tumor.</p>}},
  author       = {{Azatyan, Ani and Zhang, Shasha and Darabi, Anna and Siesjö, Peter and Wang, Ting and Zaphiropoulos, Peter G.}},
  issn         = {{2072-6694}},
  keywords     = {{Back‐spliced junction; Cerebellar tumor; CircRNA; Hedgehog pathway; RNA‐seq}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{20}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Circular rnas in hedgehog signaling activation and hedgehog‐mediated medulloblastoma tumors}},
  url          = {{http://dx.doi.org/10.3390/cancers13205138}},
  doi          = {{10.3390/cancers13205138}},
  volume       = {{13}},
  year         = {{2021}},
}