Downregulation of LncRNA OIP5-AS1 Induced by IL-1β Aggravates Osteoarthritis via Regulating miR-29b-3p/PGRN. 2021

Liqiang Zhi, and Jianwu Zhao, and Hongmou Zhao, and Zhong Qing, and Hongliang Liu, and Jianbing Ma
Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Long noncoding RNA (lncRNA) OIP5 antisense RNA 1 (OIP5-AS1) is an oncogenic lncRNA; however, its role in osteoarthritis (OA) pathology still remains unknown. qRT-PCR was performed to measure the expressions of OIP5-AS1, miR-29b-3p and progranulin (PGRN) mRNA in OA cartilage tissues and normal cartilage tissues. Chondrocyte cell lines, CHON-001 and ATDC5, were treated with different doses of interleukin-1β (IL-1β) to induce the inflammatory response. Overexpression plasmids, microRNA mimics, microRNA inhibitors and small interfering RNAs were constructed and transfected into CHON-001 and ATDC5 cells. CCK-8 assay was used for determining the cell viability and Transwell assay was used for monitoring cell migration. Western blot was applied to measure the expressions of apoptosis-related proteins. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the contents of inflammatory factors. StarBase and TargetScan were used to predict the binding sites between OIP5-AS1 and miR-29b-3p, miR-29b-3p and 3'-UTR of PGRN respectively, which were verified by dual luciferase reporter assay. OIP5-AS1 and PGRN mRNA were downregulated while miR-29b-3p was upregulated in OA tissues and models. The up-regulated OIP5-AS1 facilitated the proliferation and migration of CHON-001 and ATDC5 cells, while ameliorated the apoptosis and inflammatory response. However, miR-29b-3p had opposite effects. PGRN was identified as a target gene of miR-29b-3p, which could be indirectly suppressed by OIP5-AS1 knockdown. Downregulation of OIP5-AS1 induced by IL-1β could inhibit the proliferation and migration abilities of CHON-001 and ATDC5 cells and facilitate the apoptosis and inflammation response via regulating miR-29b-3p/PGRN axis.

UI MeSH Term Description Entries
D010003 Osteoarthritis A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. Arthritis, Degenerative,Osteoarthrosis,Osteoarthrosis Deformans,Arthroses,Arthrosis,Arthritides, Degenerative,Degenerative Arthritides,Degenerative Arthritis,Osteoarthritides,Osteoarthroses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077153 Progranulins Cysteine-rich, precursor glycoproteins encoded by the granulin gene (GRN). They contain granulin-repeats separated by linker sequences that are cleaved by a variety of proteases to release the individual GRANULIN PEPTIDES. The mammalian progranulin is composed of a half-granulin repeat followed by 7 granulin repeats. The mammalian GRANULINS are named PARAGRANULIN and granulin 1-7 for their order in the progranulin propeptide. Progranulin has growth-factor like effects and is expressed over a broad range of tissues. Under-expression of progranulin is linked to neurodegenerative diseases including FRONTOTEMPORAL DEMENTIA and NEURONAL CEROID LIPOFUSCINOSIS, while over-expression is linked to metabolic diseases including OBESITY, and INSULIN RESISTANCE. Acrogranin,Granulin Precursor,Granulin Precursor Protein,PC Cell-Derived Growth Factor,Proepithelin,Progranulin,PC Cell Derived Growth Factor
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D053583 Interleukin-1beta An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane. IL-1 beta,Catabolin,Interleukin-1 beta,Interleukin 1 beta,Interleukin 1beta
D062085 RNA, Long Noncoding A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin. LincRNA,RNA, Long Untranslated,LINC RNA,LincRNAs,Long Intergenic Non-Protein Coding RNA,Long Non-Coding RNA,Long Non-Protein-Coding RNA,Long Noncoding RNA,Long ncRNA,Long ncRNAs,RNA, Long Non-Translated,lncRNA,Long Intergenic Non Protein Coding RNA,Long Non Coding RNA,Long Non Protein Coding RNA,Long Non-Translated RNA,Long Untranslated RNA,Non-Coding RNA, Long,Non-Protein-Coding RNA, Long,Non-Translated RNA, Long,Noncoding RNA, Long,RNA, Long Non Translated,RNA, Long Non-Coding,RNA, Long Non-Protein-Coding,Untranslated RNA, Long,ncRNA, Long,ncRNAs, Long
D035683 MicroRNAs Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing. RNA, Small Temporal,Small Temporal RNA,miRNA,stRNA,Micro RNA,MicroRNA,Primary MicroRNA,Primary miRNA,miRNAs,pre-miRNA,pri-miRNA,MicroRNA, Primary,RNA, Micro,Temporal RNA, Small,miRNA, Primary,pre miRNA,pri miRNA

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