Department of Neonates, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Int J Mol Med. 2019 Oct;44(4):1399-1413. doi: 10.3892/ijmm.2019.4299. Epub 2019 Aug 2.
At present, thousands of circular RNAs (circRNAs) have been found in cancer and various tissues from different species. However, the expression of circRNAs during rat lung development remains largely unknown. In the present study, circRNA expression profiles were screened in three mixed rat lung tissues at 3 time‑points [embryonic day (E) 19, E21 and post‑natal (P) day 3] during fetal rat development with circRNA high‑throughput sequencing. Preliminary results were verified by reverse transcription‑PCR (RT‑PCR) at 4 time‑points (E16, E19, E21 and P3). A total of 375 circRNAs were differently expressed in E19 vs. E21 (fold change ≥1.5; P<0.05). At the same time, a total of 358 circRNAs were differently expressed in E21 vs. P3 (fold change ≥1.5; P<0.05). A total of 3 circRNAs (rno_circ:chr7:24777879‑24784993, rno_circ:chr14:14620910‑14624933 and rno_circ:chr3:1988750‑1998592) were characterized by having consistent fold changes (≥1.5) between 3 time‑points (E19, E21 and P3) and were selected for RT‑PCR at 4 time‑points (E16, E19, E21 and P3). Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of parent genes of the differentially expressed circRNAs revealed that these circRNAs may serve important roles in lung development. The present results support that these new found circRNAs participate in lung development. Furthermore, these findings may help to clarify the physiopathological mechanism of normal rat lung development, and may further provide a physiopathological basis of lung developmental diseases.
目前,在癌症和不同物种的各种组织中已经发现了数千种环状 RNA(circRNA)。然而,大鼠肺发育过程中 circRNA 的表达情况在很大程度上仍不清楚。本研究采用 circRNA 高通量测序技术,在大鼠胎肺发育的 3 个时间点(胚胎期 19 天(E19)、21 天(E21)和出生后 3 天(P3))筛选大鼠混合肺组织中的 circRNA 表达谱。通过在 4 个时间点(E16、E19、E21 和 P3)进行逆转录-聚合酶链反应(RT-PCR)验证了初步结果。E19 与 E21 相比,共有 375 个 circRNA 表达水平差异有统计学意义(fold change≥1.5;P<0.05)。同时,E21 与 P3 相比,共有 358 个 circRNA 表达水平差异有统计学意义(fold change≥1.5;P<0.05)。通过 RT-PCR 在 4 个时间点(E16、E19、E21 和 P3)对 3 个 circRNA(rno_circ:chr7:24777879-24784993、rno_circ:chr14:14620910-14624933 和 rno_circ:chr3:1988750-1998592)进行特征描述,发现这 3 个 circRNA 在 3 个时间点(E19、E21 和 P3)的倍数变化(≥1.5)一致,因此选择这 3 个 circRNA 进行验证。随后,对差异表达 circRNA 亲本基因进行基因本体论和京都基因与基因组百科全书分析,结果表明这些 circRNA 可能在肺发育中发挥重要作用。本研究结果支持这些新发现的 circRNA 参与肺发育的观点。此外,这些发现可能有助于阐明正常大鼠肺发育的病理生理机制,并为肺发育疾病提供病理生理基础。