Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promotes the Osteoblast Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Targeting the microRNA-96/Osterix Axis.

Abstract

OBJECTIVES:

To investigate whether and how the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) sponges microRNA-96 (miR-96) to achieve the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs).

METHODS:

Protein levels were detected by Western blot. Mineralized bone matrix formation was studied by alizarin red staining. Metastasis-associated lung adenocarcinoma transcript 1, miR-96, and osteogenesis-related Messenger RNA expression was assessed by Quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The interactions between miR-96 and osterix (Osx), MALAT1, and miR-96 were determined by luciferase reporter assay.

RESULTS:

The expression of MALAT1 was upregulated whereas that of miR-96 was downregulated in osteogenic hBMSCs. In addition, the expression of MALAT1 significantly decreased whereas that of miR-96 increased in the hBMSCs of osteoporosis (OP) patients. qRT-PCR and alizarin red staining assays showed that MALAT1 silencing or miR-96 overexpression inhibits hBMSC osteogenic differentiation and vice versa. overexpression of miR-96 reversed the promotive effect of MALAT1 on the osteogenic differentiation of hBMSCs. Dual luciferase report assay verified that miR-96 is a regulatory target of MALAT1 and that Osx is a gene target of miR-96.

CONCLUSIONS:

Taken together, the results demonstrate that MALAT1 promotes the osteogenic differentiation of hBMSCs by regulating the miR-96/Osx axis. Our study provides novel mechanistic insights into the critical role of lncRNA MALAT1 as a microRNA sponge in OP patients and sheds new light on lncRNA-directed diagnostics and therapeutics in OP.

• Authors: Lu-Yang Zang, Xiao-Lin Yang, Wei-Juan Li, Ge-Ling Liu
• Journal: The Journal of craniofacial surgery (J Craniofac Surg) Vol. 33 Issue 3 Pg. 956-961 (May 01 2022) ISSN: 1536-3732 [Electronic] United States
• PMID: 34456284 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 by Mutaz B. Habal, MD.

Chemical References

• MALAT1 long non-coding RNA, human
• MIRN96 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Sp7 Transcription Factor
• SP7 protein, human

Topics

• Bone Marrow
• Cell Differentiation (genetics)
• Cells, Cultured
• Humans
• Mesenchymal Stem Cells (cytology)
• MicroRNAs (genetics)
• Osteoblasts (cytology)
• Osteogenesis (genetics)
• Osteoporosis
• RNA, Long Noncoding (genetics)
• Sp7 Transcription Factor (genetics)