Activation ofLTBP3Gene by a Long Noncoding RNA (lncRNA)MALAT1Transcript in Mesenchymal Stem Cells from Multiple Myeloma

Abstract Synovial fluid-derived mesenchymal stem cells (SFMSCs) play important regulatory roles in the physiological balance of the temporomandibular joint. Interleukin (IL)-1β regulates the biological behavior of SFMSCs; however, the effects of IL-1β on long noncoding RNA (lncRNA) and mRNA expression in SFMSCs in the temporomandibular joint are unclear. Here, we evaluated the lncRNA and mRNA expression profiles of IL-1β-stimulated SFMSCs. Using microarrays, we identified 286 lncRNAs (222 upregulated, 64 downregulated) and 304 mRNAs (242 upregulated, 62 downregulated) that were differentially expressed after treatment with IL-1β (fold change ≥ 2, P < 0.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis found that one of the most significantly enriched pathways was the NF-κB pathway. Five paired antisense lncRNAs and mRNAs, eight paired enhancer lncRNAs and mRNAs, and nine paired long intergenic noncoding RNAs and mRNAs were predicted to be co-expressed. A network constructed by the top 30 k-score genes was visualized and evaluated. We found a co-expression relationship between ENST00000427824 and ENST00000307407 and between LOC541472 and IL6, which are related to NF-κB pathway activation. Overall, our results provide important insights into changes in lncRNA and mRNA expression in IL-1β-stimulated SFMSCs, which can facilitate the identification of potential therapeutic targets.

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Long noncoding RNA H19 regulates the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging miR-138-5p and miR-141-3p

10.21203/rs.3.rs-34046/v1 ◽

2020 ◽

Author(s):

Guodong Song ◽

Jia Zhou ◽

Ruimei Song ◽

Dalu Liu ◽

Weidi Yu ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Severe Acute Pancreatitis ◽

Long Noncoding Rna ◽

Therapeutic Efficacy ◽

Noncoding Rna ◽

Sodium Taurocholate ◽

High Morbidity

Abstract Background: Patients with severe acute pancreatitis (SAP), which is characterized by high morbidity and mortality, account for an increasing medical burden worldwide. We previously found that mesenchymal stem cells (MSCs) could attenuate SAP and that expression of long noncoding RNA H19 (LncRNA H19) was upregulated in rats receiving MSCs. In the present study, we investigated the mechanisms of LncRNA H19 regulating the therapeutic efficacy of MSCs in the alleviation of SAP.Methods: MSCs transfected with LncRNA H19 overexpression and knock down plasmids were intravenously injected into rats 12 h after sodium taurocholate (NaT) administration to induce SAP.Results: Overexpressing LncRNA H19 in MSCs significantly enhanced the anti-inflammatory capacity of the MSCs, inhibited autophagy via promotion of focal adhesion kinase (FAK)-associated pathways, and facilitated cell proliferation by increasing the level of β-catenin in rats with SAP. LncRNA H19 functioned as a competing endogenous RNA by sponging miR-138-5p and miR-141-3p. Knocking down miR-138-5p in MSCs increased the expression of protein tyrosine kinase 2 (PTK2, encoding FAK) to suppress autophagy, while downregulating miR-141-3p enhanced the level of β-catenin to promote cell proliferation.Conclusions: In conclusion, LncRNA H19 effectively increased the therapeutic efficacy of MSCs in rats with SAP via the miR-138-5p/PTK2/FAK and miR-141-3p/β-catenin pathways.

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