Exploring the CeRNA Network Involving AGAP2-AS1 As a Novel Biomarker for Preeclampsia

Overview

Journal Sci Rep

Specialty Science

Date 2024 Nov 9

PMID 39521940

Authors

Fan Lu

Ni Zeng

Xiang Xiao

Xingxing Wang

Han Gong

Houkang Lei

Affiliations

Soon will be listed here.

Abstract

Preeclampsia (PE) is an important research subject in obstetrics. Nevertheless, the underlying mechanisms of PE remain elusive. PE-related expression datasets (GSE96983, GSE96984 and GSE24129) were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differentially expressed messenger RNAs (DE-mRNAs), DE-microRNA (DE-miRNAs) and DE-long non-coding RNA (DE-lncRNAs) between PE and control cohorts were identified, and the ceRNA network was constructed. Then candidate hub genes were obtained through five algorithms by the protein-protein intersection (PPI) network of the mRNAs. Further, five hub genes were identified by receiver operating characteristic (ROC) curve and gene expression profiles: DAXX, EFNB1, NCOR2, RBBP4 and SOCS1. The function of 5 hub genes was analyzed and the interaction between drugs and hub genes was predicted. A total of 5 small molecule drugs were predicted, namely benzbromarone, 9,10-phenanthrenequinone, chembl312032, insulin and aldesleukin. AGAP2-AS1 was mainly located in exosome and cytoplasm. Agap2-as1-related regulatory subnetworks were extracted from ceRNA networks which included 41 mRNAs, 2 miRNAs and 1 lncRNA, including the regulated relationship pairs AGAP2-AS1-hsa-miR-497-5p-SRPRB, and AGAP2-AS1-hsa-miR-195-5p-RPL36. In summary, we constructed a competitive endogenous RNA (ceRNA) network to identify five potential biomarkers (DAXX, EFNB1, NCOR2, SOCS1 and RBBP4) of PE. The in-depth analysis of the AGAP2-AS1 regulatory network will help to uncover more important molecules closely related to PE and provide a scientific Reference.

References

Gustavsson E, Zhang D, Reynolds R, Garcia-Ruiz S, Ryten M . ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2. Bioinformatics. 2022; 38(15):3844-3846. PMC: 9344834. DOI: 10.1093/bioinformatics/btac409. View

Nishizawa H, Ota S, Suzuki M, Kato T, Sekiya T, Kurahashi H . Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction. Reprod Biol Endocrinol. 2011; 9:107. PMC: 3199758. DOI: 10.1186/1477-7827-9-107. View

Xu Y, Wu D, Hui B, Shu L, Tang X, Wang C . A novel regulatory mechanism network mediated by lncRNA TUG1 that induces the impairment of spiral artery remodeling in preeclampsia. Mol Ther. 2022; 30(4):1692-1705. PMC: 9077368. DOI: 10.1016/j.ymthe.2022.01.043. View

Sirico A, Rossi E, Degennaro V, Arena V, Rizzi A, Tartaglione L . Placental diabesity: placental VEGF and CD31 expression according to pregestational BMI and gestational weight gain in women with gestational diabetes. Arch Gynecol Obstet. 2022; 307(6):1823-1831. DOI: 10.1007/s00404-022-06673-3. View

Lv Y, Lu C, Ji X, Miao Z, Long W, Ding H . Roles of microRNAs in preeclampsia. J Cell Physiol. 2018; 234(2):1052-1061. DOI: 10.1002/jcp.27291. View

Rahmani F, Al-Asady A, Hanaie R, Zandigohar M, Faridnejad H, Payazdan M . Interplay between lncRNA/miRNA and Wnt/ß-catenin signaling in brain cancer tumorigenesis. EXCLI J. 2024; 22:1211-1222. PMC: 10776877. DOI: 10.17179/excli2023-6490. View

Yu G, Li F, Qin Y, Bo X, Wu Y, Wang S . GOSemSim: an R package for measuring semantic similarity among GO terms and gene products. Bioinformatics. 2010; 26(7):976-8. DOI: 10.1093/bioinformatics/btq064. View

Zhang H, Shen L . LncRNA AGAP2-AS1 in cancer: An insufficiently explored and controversial research area. Dig Liver Dis. 2023; 56(3):534. DOI: 10.1016/j.dld.2023.11.008. View

Xu Y, Xia X, Jiang Y, Wu D, Wang S, Fu S . Down-regulated lncRNA AGAP2-AS1 contributes to pre-eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype. J Cell Mol Med. 2020; 24(8):4557-4568. PMC: 7176850. DOI: 10.1111/jcmm.15113. View

10.

Peterson C, Chandler H . Insulin facilitates corneal wound healing in the diabetic environment through the RTK-PI3K/Akt/mTOR axis in vitro. Mol Cell Endocrinol. 2022; 548:111611. PMC: 9053186. DOI: 10.1016/j.mce.2022.111611. View

11.

Wu C, Li Y, Luo Y, Dai Y, Qin J, Liu N . Analysis of glutathione Stransferase mu class 5 gene methylation as a prognostic indicator in low-grade gliomas. Technol Health Care. 2024; 32(6):3925-3942. PMC: 11612950. DOI: 10.3233/THC-231316. View

12.

Mayor-Lynn K, Toloubeydokhti T, Cruz A, Chegini N . Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor. Reprod Sci. 2010; 18(1):46-56. PMC: 3343068. DOI: 10.1177/1933719110374115. View

13.

Li P, Duan S, Fu A . Long noncoding RNA NEAT1 correlates with higher disease risk, worse disease condition, decreased miR-124 and miR-125a and predicts poor recurrence-free survival of acute ischemic stroke. J Clin Lab Anal. 2019; 34(2):e23056. PMC: 7031604. DOI: 10.1002/jcla.23056. View

14.

Ding S, Wang H, Liao Y, Chen R, Hu Y, Wu H . HPV16 E7 protein antagonizes TNF-α-induced apoptosis of cervical cancer cells via Daxx/JNK pathway. Microb Pathog. 2023; 185:106423. DOI: 10.1016/j.micpath.2023.106423. View

15.

Mattick J, Amaral P, Carninci P, Carpenter S, Chang H, Chen L . Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol. 2023; 24(6):430-447. PMC: 10213152. DOI: 10.1038/s41580-022-00566-8. View

16.

Novakovic B, Evain-Brion D, Murthi P, Fournier T, Saffery R . Variable gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia. FASEB J. 2017; 31(6):2380-2392. DOI: 10.1096/fj.201601189RR. View

17.

Huang Z, Zhou J, Peng Y, He W, Huang C . The role of long noncoding RNAs in hepatocellular carcinoma. Mol Cancer. 2020; 19(1):77. PMC: 7161154. DOI: 10.1186/s12943-020-01188-4. View

18.

Drane P, Ouararhni K, Depaux A, Shuaib M, Hamiche A . The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3. Genes Dev. 2010; 24(12):1253-65. PMC: 2885661. DOI: 10.1101/gad.566910. View

19.

Raza W, Guo J, Qadir M, Bai B, Muhammad S . qPCR Analysis Reveals Association of Differential Expression of , , and Genes With Type 2 Diabetes Mellitus. Front Endocrinol (Lausanne). 2022; 12:774696. PMC: 8761634. DOI: 10.3389/fendo.2021.774696. View

20.

Adu-Gyamfi E, Czika A, Liu T, Gorleku P, Fondjo L, Djankpa F . Ephrin and Eph receptor signaling in female reproductive physiology and pathology†. Biol Reprod. 2020; 104(1):71-82. DOI: 10.1093/biolre/ioaa171. View