RGD Reference Report - LncRNA MALAT1 mediates proliferation of LPS treated-articular chondrocytes by targeting the miR-146a-PI3K/Akt/mTOR axis. - Rat Genome Database

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LncRNA MALAT1 mediates proliferation of LPS treated-articular chondrocytes by targeting the miR-146a-PI3K/Akt/mTOR axis.

Authors: Li, Hongxi  Xie, Shujuan  Li, Huazhe  Zhang, Rui  Zhang, Hanjun 
Citation: Li H, etal., Life Sci. 2020 Aug 1;254:116801. doi: 10.1016/j.lfs.2019.116801. Epub 2019 Aug 28.
RGD ID: 152177908
Pubmed: PMID:31472145   (View Abstract at PubMed)
DOI: DOI:10.1016/j.lfs.2019.116801   (Journal Full-text)

The study aimed to investigate the regulation of long noncoding RNA (lncRNA), Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in osteoarthritis (OA) development. Isolated rat chondrocytes treated with lipopolysaccharide (LPS) were used as OA cell model. Results from quantitative real-time PCR (Q-PCR) showed that, in OA patients and OA cell model, the expression of MALAT1 and PI3K was clearly reduced, while the miR-146a levels were increased. Next, MALAT1 was silenced in LPS-treated chondrocytes. Following with MALAT1 silencing, the generation of Cyclooxygenase-2 (COX-2), Interleukin-6 (IL-6) and Matrix metallopeptidase-13 (MMP-13) were promoted, while the level of type II collagen (COL2) was inhibited. Moreover, MALAT1 silencing caused a significant reduction in the proliferative rate of LPS-treated chondrocytes through inducing apoptosis. Bioinformatics prediction and dual-luciferase reporter assay (DLRA) results showed that MALAT1 targets miR-146a. MALAT1 silencing also resulted in the upregulation of miR-146a. Further studies revealed that miR-146a has the opposite effect on MALAT1, and its inhibition can antagonize the function of MALAT1 silencing on cell proliferation and apoptosis. Additionally, the 3'-UTR of the Phosphoinositide 3-kinase (PI3K) gene was found to be a target of miR-146a, while PI3K protein and mRNA expression, as well as the activation of downstream Akt and mammalian target of rapamycin (mTOR) were clearly reduced upon transfection with a miR-146a mimic. These results show that MALAT1 can modulate ECM catabolism, inflammation, and especially apoptosis in chondrocytes treated with LPS, which targets PI3K/Akt/mTOR to eventually regulate the progression of OA. Our findings provide a novel regulatory mechanism of MALAT1 in OA.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MALAT1Humanosteoarthritis  IEP mRNA:increased expression:cartilage tissue (human)RGD 
MIR146AHumanosteoarthritis  IEP mRNA:decreased expression:cartilage tissue (human)RGD 
Mir146Mouseosteoarthritis  ISOMIR146A (Homo sapiens)mRNA:decreased expression:cartilage tissue (human)RGD 
Mir146aRatosteoarthritis  ISOMIR146A (Homo sapiens)mRNA:decreased expression:cartilage tissue (human)RGD 
PIK3R1Humanosteoarthritis  IEP mRNA:increased expression:cartilage tissue (human)RGD 
Pik3r1Ratosteoarthritis  ISOPIK3R1 (Homo sapiens)mRNA:increased expression:cartilage tissue (human)RGD 
Pik3r1Mouseosteoarthritis  ISOPIK3R1 (Homo sapiens)mRNA:increased expression:cartilage tissue (human)RGD 
MALAT1Humanrheumatoid arthritis  IEP mRNA:increased expression:cartilage tissue (human)RGD 
MIR146AHumanrheumatoid arthritis  IEP mRNA:decreased expression:cartilage tissue (human)RGD 
Mir146Mouserheumatoid arthritis  ISOMIR146A (Homo sapiens)mRNA:decreased expression:cartilage tissue (human)RGD 
Mir146aRatrheumatoid arthritis  ISOMIR146A (Homo sapiens)mRNA:decreased expression:cartilage tissue (human)RGD 
PIK3R1Humanrheumatoid arthritis  IEP mRNA:increased expression:cartilage tissue (human)RGD 
Pik3r1Ratrheumatoid arthritis  ISOPIK3R1 (Homo sapiens)mRNA:increased expression:cartilage tissue (human)RGD 
Pik3r1Mouserheumatoid arthritis  ISOPIK3R1 (Homo sapiens)mRNA:increased expression:cartilage tissue (human)RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MALAT1Humanlipopolysaccharide increases expression EXP LPS increases expression of MALAT1 mRNA in chondrocytes from RA patientsRGD 
MIR146AHumanlipopolysaccharide decreases expression EXP LPS decreases expression of MIR146A mRNA in chondrocytes from RA patientsRGD 
Mir146Mouselipopolysaccharide decreases expression ISOMIR146A (Homo sapiens)LPS decreases expression of MIR146A mRNA in chondrocytes from RA patientsRGD 
Mir146aRatlipopolysaccharide decreases expression ISOMIR146A (Homo sapiens)LPS decreases expression of MIR146A mRNA in chondrocytes from RA patientsRGD 
PIK3R1Humanlipopolysaccharide increases expression EXP LPS increases expression of PIK3R1 mRNA in chondrocytes from RA patientsRGD 
Pik3r1Ratlipopolysaccharide increases expression ISOPIK3R1 (Homo sapiens)LPS increases expression of PIK3R1 mRNA in chondrocytes from RA patientsRGD 
Pik3r1Mouselipopolysaccharide increases expression ISOPIK3R1 (Homo sapiens)LPS increases expression of PIK3R1 mRNA in chondrocytes from RA patientsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir146a  (microRNA 146a)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Mus musculus)
Mir146  (microRNA 146)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Homo sapiens)
MALAT1  (metastasis associated lung adenocarcinoma transcript 1)
MIR146A  (microRNA 146a)
PIK3R1  (phosphoinositide-3-kinase regulatory subunit 1)


Additional Information