Integrative Analysis of the LncRNA-Associated CeRNA Regulatory Network Response to Hypoxia in Alveolar Type II Epithelial Cells of Tibetan Pigs

Overview

Journal Front Vet Sci

Specialty Veterinary Medicine

Date 2022 Feb 25

PMID 35211545

Authors

Yanan Yang

Yongqing Li

Haonan Yuan

Xuanbo Liu

Yue Ren

Caixia Gao

Ting Jiao

Yuan Cai

Shengguo Zhao

Affiliations

Soon will be listed here.

Abstract

The function of alveolar type II epithelial (ATII) cells is severely hampered by oxygen deficiency, and understanding the regulatory mechanisms controlling responses to hypoxia may assist in relieving injury induced by hypoxia. In this study, we cultured ATII cells from Tibetan pigs and Landrace pigs under hypoxic and normoxic environments to screen for differentially expressed (DE) lncRNAs, DEmiRNAs, and construct their associated ceRNA regulatory networks in response to hypoxia. Enrichment analysis revealed that target genes of DElncRNAs of Tibetan pigs and Landrace pig between the normoxic (TN, LN) and hypoxic (TL, LL) groups significantly enriched in the proteoglycans in cancer, renal cell carcinoma, and erbB signaling pathways, while the target genes of DEmiRNAs were significantly enriched in the axon guidance, focal adhesion, and mitogen-activated protein kinase (MAPK) signaling pathways. Hypoxia induction was shown to potentially promote apoptosis by activating the focal adhesion/PI3K-Akt/glycolysis pathway. The ssc-miR-20b/MSTRG.57127.1/ssc-miR-7-5p axis potentially played a vital role in alleviating hypoxic injury by regulating ATII cell autophagy under normoxic and hypoxic conditions. MSTRG.14861.4-miR-11971-z-CCDC12, the most affected axis, regulated numerous RNAs and may thus regulate ATII cell growth in Tibetan pigs under hypoxic conditions. The ACTA1/ssc-miR-30c-3p/MSTRG.23871.1 axis is key for limiting ATII cell injury and improving dysfunction and fibrosis mediated by oxidative stress in Landrace pigs. Our findings provide a deeper understanding of the lncRNA/miRNA/mRNA regulatory mechanisms of Tibetan pigs under hypoxic conditions.

References

Pertea M, Kim D, Pertea G, Leek J, Salzberg S . Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016; 11(9):1650-67. PMC: 5032908. DOI: 10.1038/nprot.2016.095. View

You B, Liu Y, Chen J, Huang X, Peng H, Liu Z . Vascular peroxidase 1 mediates hypoxia-induced pulmonary artery smooth muscle cell proliferation, apoptosis resistance and migration. Cardiovasc Res. 2017; 114(1):188-199. DOI: 10.1093/cvr/cvx234. View

Cui S, Yang C, Chen D . LncRNA EWSAT1 Regulates the Tumorigenesis of NSCLC as a ceRNA by Modulating miR-330-5p/ITGA5 Axis. Biochem Genet. 2021; 59(6):1441-1456. DOI: 10.1007/s10528-021-10069-4. View

Chen S, Zhou Y, Chen Y, Gu J . fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018; 34(17):i884-i890. PMC: 6129281. DOI: 10.1093/bioinformatics/bty560. View

Teng Y, Ding M, Wang X, Li H, Guo Q, Yan J . LncRNA RMRP accelerates hypoxia-induced injury by targeting miR-214-5p in H9c2 cells. J Pharmacol Sci. 2019; 142(2):69-78. DOI: 10.1016/j.jphs.2019.07.014. View

Kong L, Zhang Y, Ye Z, Liu X, Zhao S, Wei L . CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine. Nucleic Acids Res. 2007; 35(Web Server issue):W345-9. PMC: 1933232. DOI: 10.1093/nar/gkm391. View

Xiao H . MiR-7-5p suppresses tumor metastasis of non-small cell lung cancer by targeting NOVA2. Cell Mol Biol Lett. 2019; 24:60. PMC: 6864997. DOI: 10.1186/s11658-019-0188-3. View

Yang Y, Gao C, Yang T, Sha Y, Cai Y, Wang X . Characteristics of Tibetan pig lung tissue in response to a hypoxic environment on the Qinghai-Tibet Plateau. Arch Anim Breed. 2021; 64(1):283-292. PMC: 8253108. DOI: 10.5194/aab-64-283-2021. View

Bernard O, Jeny F, Uzunhan Y, Dondi E, Terfous R, Label R . Mesenchymal stem cells reduce hypoxia-induced apoptosis in alveolar epithelial cells by modulating HIF and ROS hypoxic signaling. Am J Physiol Lung Cell Mol Physiol. 2017; 314(3):L360-L371. DOI: 10.1152/ajplung.00153.2017. View

10.

Lu Y, Wang S, Cai S, Gu X, Wang J, Yang Y . Propofol-induced MiR-20b expression initiates endogenous cellular signal changes mitigating hypoxia/re-oxygenation-induced endothelial autophagy in vitro. Cell Death Dis. 2020; 11(8):681. PMC: 7442825. DOI: 10.1038/s41419-020-02828-9. View

11.

Choi H, Sanders T, Tormos K, Ameri K, Tsai J, Park A . ECM-dependent HIF induction directs trophoblast stem cell fate via LIMK1-mediated cytoskeletal rearrangement. PLoS One. 2013; 8(2):e56949. PMC: 3578927. DOI: 10.1371/journal.pone.0056949. View

12.

Morimoto C, Takedachi M, Kawasaki K, Shimomura J, Murata M, Hirai A . Hypoxia stimulates collagen hydroxylation in gingival fibroblasts and periodontal ligament cells. J Periodontol. 2021; 92(11):1635-1645. DOI: 10.1002/JPER.20-0670. View

13.

Ai H, Fang X, Yang B, Huang Z, Chen H, Mao L . Adaptation and possible ancient interspecies introgression in pigs identified by whole-genome sequencing. Nat Genet. 2015; 47(3):217-25. DOI: 10.1038/ng.3199. View

14.

Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J . STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2014; 43(Database issue):D447-52. PMC: 4383874. DOI: 10.1093/nar/gku1003. View

15.

Yang Y, Gao C, Yang T, Sha Y, Cai Y, Wang X . Vascular characteristics and expression of hypoxia genes in Tibetan pigs' hearts. Vet Med Sci. 2021; 8(1):177-186. PMC: 8788992. DOI: 10.1002/vms3.639. View

16.

Li J, Chen D, Yu B, He J, Huang Z, Mao X . The fungal community and its interaction with the concentration of short-chain fatty acids in the faeces of Chenghua, Yorkshire and Tibetan pigs. Microb Biotechnol. 2019; 13(2):509-521. PMC: 7017814. DOI: 10.1111/1751-7915.13507. View

17.

Sulkowska M . Morphological studies of the lungs in chronic hypobaric hypoxia. Pol J Pathol. 1997; 48(4):225-34. View

18.

Saad A, Zhu X, Herrmann S, Hickson L, Tang H, Dietz A . Adipose-derived mesenchymal stem cells from patients with atherosclerotic renovascular disease have increased DNA damage and reduced angiogenesis that can be modified by hypoxia. Stem Cell Res Ther. 2016; 7(1):128. PMC: 5016873. DOI: 10.1186/s13287-016-0389-x. View

19.

Li W, Ma S, Bai X, Pan W, Ai L, Tan W . Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer. J Cell Physiol. 2019; 235(2):1141-1154. DOI: 10.1002/jcp.29028. View

20.

Ma Y, Han X, Huang C, Zhong L, Adeola A, Irwin D . Population Genomics Analysis Revealed Origin and High-altitude Adaptation of Tibetan Pigs. Sci Rep. 2019; 9(1):11463. PMC: 6685962. DOI: 10.1038/s41598-019-47711-6. View