Abstract

Formaldehyde exposure during pregnancy can cause fetal congenital heart disease (CHD). However, the regulatory mechanism remains unclear. Studies on the biology of long non-coding RNAs (lncRNAs) show that lncRNAs can influence cardiac development and disease. However, expression patterns and regulatory mechanisms of action of lncRNAs in formaldehyde-induced CHD remain unclear. We used high-throughput sequencing strategies as a means of identifying lncRNA expression profiles in heart tissues of normal and formaldehyde-exposed newborn rats. Overall, 763 differentially expressed lncRNAs were identified, including 325 and 438 that were respectively up-regulated and down-regulated. GO and KEGG analyses indicated that the Ras and hedgehog signaling pathways may be important regulatory pathways in CHD caused by exposure to formaldehyde. A lncRNA-miRNA-mRNA co-expression network was constructed and a key miRNA , rno-miR-665, was identified. Furthermore, qRT-PCR analysis verified that the novel lncRNAs: MSTRG.27313.2, MSTRG.30629.2, MSTRG.36520.33, MSTRG.91234.1, and MSTRG.91233.9, were upregulated in the formaldehyde-exposed group. These differentially expressed lncRNAs identified during formaldehyde-induced CHD in newborn rats help explain CHD pathogenesis and provide an effective reference for diagnosing and treating CHD.