Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov;105(11):1939-1949.
doi: 10.1113/EP088780. Epub 2020 Oct 7.

Involvement of the lncRNA AFAP1-AS1/microRNA-195/E2F3 axis in proliferation and migration of enteric neural crest stem cells of Hirschsprung's disease

Weikang Pan  1 , Ali Wu  2 , Hui Yu  1 , Qiang Yu  1 , Baijun Zheng  1 , Weili Yang  1 , Donghao Tian  1 , Peng Li  1 , Ya Gao  1
Affiliations
Free article

Involvement of the lncRNA AFAP1-AS1/microRNA-195/E2F3 axis in proliferation and migration of enteric neural crest stem cells of Hirschsprung's disease

Weikang Pan et al. Exp Physiol. 2020 Nov.
Free article

Abstract

New findings: What is the central question of this study? Long non-coding RNAs (lncRNAs) are widely involved in the progression of Hirschsprung's disease (HSCR), but the role of actin filament associated protein 1 antisense RNA1 (AFAP1-AS1), an lncRNA, in HSCR has not been explored before. What is the main finding and its importance? Downregulation of AFAP1-AS1 blocks enteric neural crest stem cell proliferation, differentiation, migration and invasion and promotes the occurrence of HSCR via the miR-195/E2F3 axis, indicating thatAFAP1-AS might be a potential biomarker for HSCR patients.

Abstract: Long non-coding RNAs (lncRNAs) are involved in several human disorders. Nevertheless, it remains unclear whether they are implicated in the phenotypes of enteric neural crest stem cells (ENCSCs) in Hirschsprung's disease (HSCR). Therefore, we designed this study to explore the pathogenicity of AFAP1-AS1 for HSCR. Microarray analysis and bioinformatic tools were used to screen out the differentially lncRNAs and microRNAs (miRNAs) in patients with HSCR. Small interference RNA transfection was applied to carry out functional experiments in ENCSCs. Cellular activities were detected by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Transwell assays and flow cytometry. Finally, rescue experiments were performed to examine the cofunction of AFAP1-AS1 and miR-195 and of miR-195 and E2F transcription factor 3 (E2F3). AFAP1-AS1 was reduced in HSCR patients. Meanwhile, knockdown of AFAP1-AS1 reduced the cell migratory and proliferative capacities and facilitated cell apoptosis along with G0/G1 phase arrest. E2F3 was diminished when miR-195 was upregulated, and AFAP1-AS1 inhibition reduced its ability to bind to miR-195. Altogether, AFAP1-AS1 silencing acts as an endogenous RNA by interacting with miR-195 to alter E2F3 expression, thus conferring repressive effects on ENCSC activity and promoting HSCR progression.

Keywords: E2F transcription factor 3; Hirschsprung's disease; enteric neural crest stem cells; long non-coding RNA AFAP1-AS1; microRNA-195.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. Andrusiak, M. G., McClellan, K. A., Dugal-Tessier, D., Julian, L. M., Rodrigues, S. P., Park, D. S., … Slack, R. S. (2011). Rb/E2F regulates expression of neogenin during neuronal migration. Molecular and Cellular Biology, 31, 238-247.
    1. Bai, J., Xu, J., Zhao, J., & Zhang, R. (2020). lncRNA SNHG1 cooperated with miR-497/miR-195-5p to modify epithelial-mesenchymal transition underlying colorectal cancer exacerbation. Journal of Cellular Physiology, 235, 1453-1468.
    1. Batista, P. J., & Chang, H. Y. (2013). Long noncoding RNAs: Cellular address codes in development and disease. Cell, 152, 1298-1307.
    1. Chen, G., Peng, L., Zhu, Z., Du, C., Shen, Z., Zang, R., … Tang, W. (2017). LncRNA AFAP1-AS functions as a competing endogenous RNA to regulate RAP1B expression by sponging miR-181a in the HSCR. International Journal of Medical Sciences, 14, 1022-1030.
    1. Cheng, L. S., Hotta, R., Graham, H. K., Nagy, N., Goldstein, A. M., & Belkind-Gerson, J. (2015). Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease. Neurogastroenterology and Motility, 27, 1509-1514.

Publication types

MeSH terms