Crosstalk of mRNA, miRNA, lncRNA, and circRNA and Their Regulatory Pattern in Pulmonary Fibrosis

Abstract

Noncoding RNAs (ncRNAs), such as microRNA (miRNA), long ncRNA (lncRNA), and circular RNA (circRNA), are regulators of important biological functions. Therefore, understanding their crosstalk and regulatory patterns can provide treatment for diseases. In this study, differentially expressed RNA transcripts were obtained by RNA sequencing in bleomycin-induced pulmonary fibrosis in mice. Four miRNAs, 10 lncRNAs, and two circRNAs were tested to validate the sequencing. There were differentially expressed 585 mRNAs, 236 miRNAs, 272 lncRNAs, and 74 circRNAs in pulmonary fibrosis. Their location on chromosome, length varieties, interaction, and host genes were analyzed. lnc949, circ949, and circ057 were chosen to explore the detailed crosstalk and regulatory pattern, which were measured by using RNA-FISH, dual-luciferase reporter assay, real-time cell analysis and rescue experiment, co-localization analysis, RNA immunoprecipitation, and RNA pull down. The data showed that the three ncRNAs were predominant in the cytoplasm, and their regulatory patterns were focused on post-transcription. The fibrotic function of lnc949 depended on its host gene FKBP5. circ949 and circ057 formed a regulatory network with lnc865 and lnc556 to simultaneously regulate miR-29b-2-5p targeting STAT3 phosphorylation. Collectively, different RNAs can crosstalk with each other to regulate pulmonary fibrosis through different regulatory patterns. We hope these data can provide a full concept of RNA transcripts, leading to a new treatment for pulmonary fibrosis.

RETRACTED: LncRNA CCDC26 Interacts with CELF2 Protein to Enhance Myeloid Leukemia Cell Proliferation and Invasion via the circRNA_ANKIB1/miR-195-5p/PRR11 Axis

“…In intervertebral disc degeneration, multiple competitive endogenous RNA (ceRNA) networks were obtained, such as the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/circRNA_102348/miR-185-5p/transforming growth factor-beta 1 (TGFB1) axis, the circRNA_102399/miR-302a-3p/hypoxia-inducible factor 1 subunit alpha (HIF1A) axis, and the circRNA_100086/miR-509-3p/ mitogen-activated protein kinase 1 (MAPK1) axis, etc 16 . In pulmonary fibrosis, circRNA_949 (chromosome 14: 30346797-30350949) and circRNA_057 (chromosome 6:99003199-99100057) form a regulatory network with lncRNA NONMMUT039865 and lncRNA NONMMUT039556, simultaneously regulating miR-29b-2-5p targeting signal transducer and activator of transcription 3 (STAT3) phosphorylation in a bleomycin-induced mouse model 17 .…”

Engeletin ameliorates pulmonary fibrosis through endoplasmic reticulum stress depending on lnc949-mediated TGF-β1-Smad2/3 and JNK signalling pathways

“…LncRNA-NONMMUT028949.2 (lnc949) has a remarkably high expression in pulmonary fibrosis according to our previous study (Li et al. 2019 ). Thus, lnc949 was chosen to further identify the lncRNA regulation of engeletin during its drug action.…”

“…Lnc949-mediated TGF-b1-Smad2/3 and JNK were the upstream signalling pathways of ER stress induced by engeletin Long noncoding RNA (lncRNA) is a class of noncoding gene that regulates protein-coding genes in their upstream signalling pathways. LncRNA-NONMMUT028949.2 (lnc949) has a remarkably high expression in pulmonary fibrosis according to our previous study (Li et al 2019). Thus, lnc949 was chosen to further identify the lncRNA regulation of engeletin during its drug action.…”

Circular RNA cMTO1 Promotes PTEN Expression Through Sponging miR-181b-5p in Liver Fibrosis

“…For instance, cir-ITCH acts as a tumor suppressor in esophageal squamous cell carcinoma via sponging miR-7, miR-17, and miR-214 (Li F. et al, 2015). In addition, circRNAs have been reported to be involved in the progression of fibrotic diseases such as cardiac fibrosis and pulmonary fibrosis (Li et al, 2019;Gu et al, 2020). Herein, we found that cMTO1 participated in the progression of liver fibrosis.…”