Effect Of XBP1 Deficiency In Cartilage On The Regulatory Network Of LncRNA/circRNA-miRNA-mRNA

Abstract

X-box binding protein 1(XBP1) is a critical component for unfolded protein response (UPR) in ER stress. According to previous studies performed with different XBP1-deficient mice, the XBP1 gene affects mouse cartilage development and causes other related diseases. However, how the complete transcriptome, including mRNA and ncRNAs, affects the function of cartilage and other tissues when XBP1 is deficient in chondrocytes is unclear. In this study, we aimed to screen the differentially expressed (DE) mRNAs, circRNAs, lncRNAs and miRNAs in XBP1 cartilage-specific knockout (CKO) mice using high throughput sequencing and construct the circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA regulatory networks. DE LncRNAs (DE-LncRNAs), circRNAs (DE-circRNAs), miRNAs (DE-miRNAs), and mRNAs [differentially expressed genes (DEGs)] between the cartilage tissue of XBP1 CKO mice and controls were identified, including 441 and 477 DEGs. Further, 253,235 lncRNA-miRNA-mRNA networks and 1,822 circRNA-miRNA-mRNA networks were constructed based on the correlation between lncRNAs/circRNAs, miRNAs, mRNAs. The whole transcriptome analysis revealed that XBP1 deficiency in cartilage affects the function of cartilage and other different tissues, as well as associated diseases. Overall, our findings may provide potential biomarkers and mechanisms for the diagnosis and treatment of cartilage and other related diseases.

CircLDLRAD3 inhibits Oral squamous cell carcinoma progression by regulating miR‐558/Smad4/TGF‐β

“…In recent years, it has been well documented that circRNAs can absorb miRNAs through sponge action, affecting the level of miRNAs, which in turn regulates the expression of related miRNA‐targeted genes and ultimately exerts a pro‐ or anti‐cancer effect 30,34–36 . In the present study, we confirmed that circLDLRAD3 could inhibit the malignant biological function of squamous cancer cells, and we speculated that it might act through an endogenously competitive mechanism.…”

“…In recent years, it has been well documented that circRNAs can absorb miRNAs through sponge action, affecting the level of miRNAs, which in turn regulates the expression of related miRNA-targeted genes and ultimately exerts a pro-or anti-cancer effect. 30,[34][35][36] In the present study, we confirmed that circLDLRAD3 could inhibit the malignant biological function of squamous cancer cells, and we speculated that it might act through an endogenously competitive mechanism. Through the combination of a series of bioinformatic analysis and experimental results, our study found that miR-558 was significantly decreased after overexpression of circLDLRAD3, while increased upon circLDLRAD3 knockdown.…”

Identification of a Novel Angiogenesis Signalling circSCRG1/miR-1268b/NR4A1 Pathway in Atherosclerosis and the Regulatory Effects of TMP-PF In Vitro

“…Bioinformatic analysis was performed to screen the DE circRNAs and DE mRNAs with cut-offs of p ≤ 0.05 and |FC| ≥ 2. circRNA-miRNA and miRNA–mRNA interactions were predicted with the miRanda, RNAhybrid and TargetScan databases. The overlapping miRNAs predicted as downstream targets of the DE circRNAs and upstream regulators of the DE mRNAs were enriched, and then the DE circRNA-miRNA-mRNA networks involved in atherosclerosis were established as described in a previous study [ 43 ]. Then, angiogenesis-related mRNAs were used to establish atherosclerosis-related circRNA-miRNA-mRNA networks that regulate angiogenesis, and candidate circRNAs were preliminarily identified.…”

Novel insights into the multifaceted roles of m6A-modified LncRNAs in cancers: biological functions and therapeutic applications

“…A multitude of lowly expressed and often nonconserved lncRNAs were pervasively identified in transcripts of human cancer genome [ 12 ] [ 13 ] [ 14 ] [ 15 ]. Lots of studies further proved that lncRNAs were recurrently deregulated in cancers and functioned as tumor suppressors or oncogenes through sponging miRNAs [ 16 , 17 ]. Moreover, mechanism researches revealed that lncRNAs acted an essential role in numerous pathways including p53 [ 18 ], STAT3 [ 19 ] and mTOR [ 20 ] cascades.…”