Knockdown of long non-coding RNA HOTAIR promotes bone marrow mesenchymal stem cell differentiation by sponging microRNA miR-378g that inhibits nicotinamide N-methyltransferase

Wang, Wei; Li, Tao; Feng, Shibo

doi:10.1080/21655979.2021.2006863

Cited by 11 publications

(6 citation statements)

References 46 publications

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“…Bioinformatic analyses conducted in the current study preliminarily predicted that miR-378g is a miRNA directly targeted by PAX8-AS1. A previous study has confirmed that miR-378g promotes the osteogenic differentiation of bone marrow mesenchymal stem cells after escaping from the inhibition caused by HOTAIR [ 27 ]. HOTAIR confers ADM resistance in AML [ 13 ].…”

Section: Introductionmentioning

confidence: 93%

LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia via the miR-378g/ERBB2 Axis

Song

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Considering the role of lncRNAs reported as regulators in acute myeloid leukemia (AML) progression, the current research aims to investigate the role of PAX8-AS1 in chemo-resistant AML. Methods. Human AML cells HL60 and human doxorubicin (ADM)-resistant AML cells (HL60/ADM cells) were used to establish in vitro models of chemo-sensitive AML and refractory/recurrent AML, respectively. CCK-8 assay and flow cytometry were used to determine cell resistance to ADM, viability, and apoptosis. PAX8-AS1, miR-378g, and ERBB2 expressions in the models and/or AML patients were quantified via qRT-PCR or Western blot. The miRNA/mRNA axis targeted by PAX8-AS1 was analyzed using Starbase, TargetScan, or GEO and validated through a dual-luciferase reporter assay. The expressions of Bcl-2, Bax, and C Caspase-3 in cells were quantitated by Western blot. Results. The highly expressed PAX8-AS1 was observed in AML patients and HL60 cells, which was more evident in refractory/recurrent AML patients and HL60/ADM cells. Compared with that in ADM-treated parental HL60 cells, the viability of ADM-treated HL60/ADM cells remained strong. PAX8-AS1 overexpression increased viability and Bcl-2 expression, while diminishing apoptosis, Bax, and C Caspase-3 expressions in HL60 cells. However, the abovementioned aspects were oppositely impacted by PAX8-AS1 silencing in HL60/ADM cells. PAX8-AS1 directly targeted miR-378g, whose expression pattern is opposite to that of PAX8-AS1 in AML. MiR-378g upregulation abrogated the effects of PAX8-AS1 overexpression on HL60 cells. MiR-378g downregulation offset PAX8-AS1 silencing-induced effects on HL60/ADM cells. Moreover, ERBB2 was recognized as the target of miR-378g, with a higher expression in HL60/ADM cells than in HL60 cells. Conclusion. PAX8-AS1 silencing decreases cell viability, enhances apoptosis, and suppresses ADM resistance in AML via regulating the miR-378g/ERBB2 axis.

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Section: Introductionmentioning

confidence: 93%

LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia via the miR-378g/ERBB2 Axis

Song

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Patients with the HOTAIR rs7958904 CC genotype had significantly lower CD19 levels than patients with the HOTAIR rs7958904 GG and GC genotypes ( p = 0.032; Table S7 , Figure S1 ). Abnormal HOTAIR expression has also been reported in development of various diseases [ 29 , 30 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

Association of Polymorphisms in the Long Non-Coding RNA HOTAIR with Recurrent Pregnancy Loss in a Korean Population

Park

Kim

Lee

et al. 2022

Genes

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Recurrent pregnancy loss (RPL) affects 1% to 5% of women, with devastating effects on both reproductive health and psychological well-being. Homeobox (HOX) transcript antisense RNA (HOTAIR) is a long non-coding RNA (lncRNA) produced by HOXC; it plays a major role in invasion and development of ovarian and other cancers. The aim of the present study was to analyze effects of HOTAIR polymorphisms (rs4759314 A>G, rs920778 T>C, rs1899663 G>T, and rs7958904 G>C) on RPL in Korean women. A total of 403 women with RPL and 383 healthy women were selected for this study. Genotyping analysis was performed with the polymerase chain reaction, restriction fragment length polymorphism, and the TaqMan genotyping assay. Clinical characteristics were compared using Student’s unpaired t-test and the chi-square test for categorical variables. Logistic regression was performed to evaluate associations between single nucleotide polymorphisms and RPL incidence. In all assays, p < 0.05 was considered significant. HOTAIR polymorphisms rs4759314A>G and rs920778T>C were highly associated with increased risk of RPL, specifically the haplotypes rs4759314A>G/rs1899663G>T (G-T) and rs4759314A>G/rs920778 T>C (G-C). These associations were maintained in haplotypes that contained three polymorphisms (rs4759314 A>G, rs920778 T>C, and rs1899663 G>T) A-C-G, G-T-G, and G-T-T, further indicating that the HOTAIR rs4759314 and rs920778 polymorphisms play significant roles in idiopathic RPL in Korean women.

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“…MiRNAs are small noncoding RNAs that regulate gene expression via recognition of cognate sequences and interference of transcriptional, translational or epigenetic processes ( Chen L. et al, 2019 ), miRNAs control mRNA expression, miRNAs are also capable of targeting non-coding RNAs, including long non-coding RNAs and miRNAs ( Hill and Tran, 2021 ). Recently Yu et al ( Yu et al, 2021 ) and Wang et al ( Wang et al, 2021 ) identified miR-29b-3p and miR-378g as potential miRNAs upstream of NNMT by bioinformatics analysis. It was confirmed by dual luciferase reporter assay that miR-29b-3p and miR-378g directly target the 3′UTR of NNMT and negatively regulate NNMT expression.…”

Section: Nnmt As a Therapeutic Target For Metsmentioning

confidence: 99%

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome

Sun,

Zhu,

et al. 2024

Front. Pharmacol.

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Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.

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Knockdown of long non-coding RNA HOTAIR promotes bone marrow mesenchymal stem cell differentiation by sponging microRNA miR-378g that inhibits nicotinamide N-methyltransferase

Cited by 11 publications

References 46 publications

LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia via the miR-378g/ERBB2 Axis

LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia via the miR-378g/ERBB2 Axis

Association of Polymorphisms in the Long Non-Coding RNA HOTAIR with Recurrent Pregnancy Loss in a Korean Population

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome

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