LncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells by targeting miR-150-5p

Abstract

Osteoporosis (OP) is a systemic bone metabolic disease with complicated pathogenesis and is difficult to cure clinically. The regulatory mechanisms of OP are needed to be further investigated. In the present study, we focused on the role of myocardial infarction-associated transcript (MIAT) in OP development and examined the underlying mechanism. The serum expression levels of MIAT in samples from patients with OP and healthy controls were compared using quantitative reverse transcription-PCR (qRT-PCR). The dual-luciferase reporter assay was used to confirm the relationship between MIAT and its potential target microRNA, i.e., miR-150-5p. Moreover, bone marrow-derived mesenchymal stem cells (BMSCs) were cultured and transfected with MIAT shRNA, with or without miR-150-5p inhibitor. EdU staining and colony formation analysis were performed to determine the proliferation ability of these cells. Furthermore, the TUNEL assay and flow cytometry were used to assess BMSC apoptosis. Finally, RT-PCR and Western blot assays were employed to assess the expression of osteogenic differentiation biomarkers. Compared with controls, the expression of MIAT was significantly increased, whereas that of miR-150-5p was markedly decreased in patients with OP. MIAT and miR-150-5p expression levels exhibited a strong negative correlation. Furthermore, osteogenic differentiation indicators were suppressed in serum of OP patients. MIAT was downregulated, and miR-150-5p was upregulated in induced to osteogenic differentiation BMSCs. Furthermore, downregulation of MIAT dramatically promoted osteogenic differentiation, increased proliferation, and inhibited apoptosis in BMSCs; miR-150-5p inhibitor abrogated the effects of MIAT. In conclusion, lncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of BMSCs.

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

“…Their presence in E-CD133 N-EVs and N-cells was confirmed by RT-qPCR ( Supplementary Figure S3 ), and their putative targets will be discussed later. Additionally, we found in E-CD133 N-EVs miRNAs that may be involved in the control of cancer cell growth, migration and/or maintenance of the stem cell-like phenotype, e.g., miR-4516 [ 48 , 49 ], miR-4286 [ 50 , 51 ], miR-150-5p [ 52 ], miR-1275 [ 53 ]; angiogenesis, e.g., miR-4286 [ 54 ]; osteogenesis, e.g., miR-4286 [ 54 ], miR-150-5p [ 55 ], miR-548d-5p [ 56 ]; and wound healing, e.g., miR-150-5p [ 57 ]. Moreover, miR150-5p-enriched exosomes derived from bone marrow mesenchymal stromal cells also demonstrated a protective effect in cerebral ischemia/reperfusion injury [ 58 ].…”

LncRNA growth arrest specific transcript 5 inhibits the growth of pituitary neuroendocrine tumors via miR-27a-5p/cylindromatosis axis

“…The dual-luciferase assay was performed as previously described [ 17 ]. The wild-type (WT) or mutant lncRNA GAS5 or CYLD 3’ UTR containing the binding sites with miR-27a-5p was cloned into pmirGLO luciferase vector (Promega, Madison, WI, USA) separately.…”

Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

“…In patients with osteoporosis, expression of the lncRNA MIAT is increased significantly when miR-150-5p is downregulated, and the serum indicators of osteogenic differentiation are decreased. 281 In addition, lncRNAs can help regulate BMSCs by binding to other molecules. RAD51-AS1, which is mainly located in the nucleus, presents low expression in BMSCs of patients with osteoporosis.…”