Circular RNA expression profiling identifies hsa_circ_0011460 as a novel molecule in severe preeclampsia.

OBJECTIVES

To identify circRNA expression profiles in the placentae of severe preeclampsia (SPE) and normal pregnant (NP) women.

METHODS

Placental samples were collected from six paired SPE and NP women. CircRNA expression profiles were identified by RNA-Seq and validated in another 30 SPE and NP samples by qRT-PCR. Several bioinformatic tools were utilised to analyse the potential function of differentially expressed circRNAs (DE-circRNAs) and to predict target microRNAs (miRNAs) and proteins. Furthermore, immunohistochemistry, Western blotting and RNA binding protein immunoprecipitation (RIP) were conducted to confirm the interaction between the circRNA and protein.

RESULTS

In total, 18,631 circRNAs were detected. Among them, 180 circRNAs were differentially expressed, including 94 upregulated and 86 downregulated circRNAs. Seven DE-circRNAs were selected for validation, and the results of six circRNAs (hsa_circ_0007611, hsa_circ_0011460, hsa_circ_0002888, and hsa_circ_0007445, hsa_circ_0017068, hsa_circ_0012737) were consistent with the sequencing results. Bioinformatics analyses of DE-circRNAs revealed that most of them are involved in vasodilation, regulation of blood vessel size, protein transport and localization, and pathways in cancer. In addition to the mRNA expression profile, it was interesting to find that the hsa_circ_0011460 target gene solute carrier organic anion transporter family member 2A1 (SLCO2A1, PGT) was also significantly increased in SPE placentae. Immunohistochemistry, Western blotting and qRT-PCR validated the expression and distribution of PGT. Finally, RIP of HTR-8/SVneo cells confirmed that hsa_circ_0011460 targets PGT directly.

CONCLUSIONS

A total of 180 DE-circRNAs were detected. One crucial circRNA, hsa_circ_0011460, was shown to interact directly with its host gene PGT. These findings indicated that hsa_circ_0011460 may serve as a potential therapeutic target for patients with SPE.