Long noncoding RNA expression profile reveals lncRNAs signature associated with extracellular matrix degradation in kashin-beck disease

Abstract

Kashin-Beck disease (KBD) is a deformative, endemic osteochondropathy involving degeneration and necrosis of growth plates and articular cartilage. The pathogenesis of KBD is related to gene expression and regulation mechanisms, but long noncoding RNAs (lncRNAs) in KBD have not been investigated. In this study, we identified 316 up-regulated and 631 down-regulated lncRNAs (≥ 2-fold change) in KBD chondrocytes using microarray analysis, of which more than three-quarters were intergenic lncRNAs and antisense lncRNAs. We also identified 232 up-regulated and 427 down-regulated mRNAs (≥ 2-fold change). A lncRNA-mRNA correlation analysis combined 343 lncRNAs and 292 mRNAs to form 509 coding-noncoding gene co-expression networks (CNC networks). Eleven lncRNAs were predicted to have cis-regulated target genes, including NAV2 (neuron navigator 2), TOX (thymocyte selection-associated high mobility group box), LAMA4 (laminin, alpha 4), and DEPTOR (DEP domain containing mTOR-interacting protein). The differentially expressed mRNAs in KBD significantly contribute to biological events associated with the extracellular matrix. Meanwhile, 34 mRNAs and 55 co-expressed lncRNAs constituted a network that influences the extracellular matrix. In the network, FBLN1 and LAMA 4 were the core genes with the highest significance. These novel findings indicate that lncRNAs may play a role in extracellular matrix destruction in KBD.

LncRNA‐ENST00000501520 promotes the proliferation of malignant‐transformed BEAS‐2B cells induced with coal tar pitch mediated by target genes

“…Molecular biological network can predict molecular interactions according to gene expression patterns, which reflects the relationship between gene expression and regulation . Present study showed that LncRNAs could form double strands with relevant miRNAs, which influenced the function of mRNAs by regulating miRNAs .…”

Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease compared with osteoarthritis

“…Laminins are a family of heterotrimeric ECM proteins 33 . Previous studies have shown the expressions of specific laminins were differentially regulated during development, adhesion, migration and regeneration [34][35][36] . In our study, LAMA2 was observed to be up-regulated in KBD group in comparison to OA.…”

Selenium-Related Transcriptional Regulation of Gene Expression

“…Analysis of mitochondria-related genes identified nine more up-regulated genes in Kashin-Beck disease versus normal control involved in three canonical pathways of oxidative phosphorylation, apoptosis signaling and pyruvate metabolism [97]. Expression profiles in cultured chondrocytes revealed 232 up-and 427 down-regulated mRNAs and 316 up-and 631 down-regulated lncRNAs [98]. A lncRNA-mRNA correlation analysis yielded 509 coding-noncoding gene co-expression networks, and eleven lncRNAs were predicted to have cis-regulated target genes, and co-expressed mRNAs and lncRNAs formed large network associated with the biological events of extracellular matrix [98].…”

“…Expression profiles in cultured chondrocytes revealed 232 up-and 427 down-regulated mRNAs and 316 up-and 631 down-regulated lncRNAs [98]. A lncRNA-mRNA correlation analysis yielded 509 coding-noncoding gene co-expression networks, and eleven lncRNAs were predicted to have cis-regulated target genes, and co-expressed mRNAs and lncRNAs formed large network associated with the biological events of extracellular matrix [98].…”