Clinical significance and biological effect of ZFAS1 in Hirschsprung's disease and preliminary exploration of its underlying mechanisms using integrated bioinformatics analysis.

BACKGROUND: The pathogenesis of Hirschprung's disease (HSCR) remains largely unknown. The lncRNA ZNFX1 antisense RNA 1 (ZFAS1) has been found to have vital regulatory roles in a number of diseases. However, the association between ZFAS1 and HSCR has not been reported.

AIMS: The present study was aimed at investigating the expression pattern and biological function and underlying mechanisms of ZFAS1 in HSCR.

METHODS: The expression of ZFAS1 was detected in surgical excision samples of 30 children diagnosed with HSCR and 30 control cases. Functional experiments were conducted after over-expression or knockdown of ZFAS1 in human neuronal cell line SH-SY-5Y. Multiple bioinformatics databases and tools were used to explore the potential regulatory mechanisms of ZFAS1 in HSCR.

RESULTS: Compared with the control group, the HSCR group has a significantly higher level of ZFAS1(P = 0.0012). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.7133 (P = 0.0045), which indicated good biomarker potency of ZFAS1 in HSCR. Functionally, over-expression of ZFAS1 significantly inhibited cell proliferation, whereas knockdown of ZFAS1 promoted cell proliferation and colony formation of SH-SY-5Y cells. Using multiple databases, a competing endogenous RNA (ceRNA) network, containing ZFAS1,13 candidate miRNAs, and 110 potential gene targets, was established. Further enrichment analysis suggested that ZFAS1 may regulate a number of genes and signaling pathways that were crucial for neuron development.

CONCLUSIONS: Our findings revealed that ZFAS1 may participate in the pathogenesis of HSCR through regulating neuron functions. Bioinformatics analysis highlighted an important perspective for the following mechanical researches.