• AIM2
• AIM2-based gene therapy
• cancer
• inflammasome
• natural and synthetic AIM2-targeted inhibitors
• single-stranded DNA
• ssDNA
• therapeutic strategies

• Cancer
• Inflammasomes
• Inflammation
• Innate immunity
• Pattern recognition receptors

• AIM2 Inflammasome
• Cytosolic DNA
• DNA-RNA Hybrids
• Immunotherapy
• PD-L1
• Pyroptosis

• Humans
• Inflammasomes/metabolism
• Nucleic Acids/therapeutic use
• Neoplasms/drug therapy
• DNA
• RNA
• DNA-Binding Proteins/metabolism

• Cancer immunology
• Immune response
• Immunotherapy
• Inflammasomes
• Pyroptosis

• AIM2 inflammasome
• cytosolic DNA
• inflammasome
• innate immunity
• tumor microenvironment

• Humans
• Inflammasomes/metabolism
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Caspase 1/metabolism
• Tumor Microenvironment
• DNA-Binding Proteins/metabolism
• Macrophages
• DNA/metabolism
• Neoplasms/metabolism
• Carcinogenesis/metabolism

• Ministry of Education - Singapore

• Immunity
• Inflammasome
• NLRP3
• Pyroptosis
• Tumor microenvironment

• Humans
• Inflammasomes
• Tumor Microenvironment
• Interleukin-1
• Inflammation

• No. 32122052 National Science Fund for Excellent Young Scholars
• No. U19A2003 National Natural Science Foundation Regional Innovation and Development

• Cytokines/genetics
• DNA
• DNA Copy Number Variations
• DNA-Binding Proteins/metabolism
• Humans
• Immunologic Factors
• Immunotherapy
• Inflammasomes/metabolism
• Melanoma/genetics
• Melanoma/therapy
• Tumor Microenvironment/genetics

• AIM2
• AIM2 inflammasome
• pathogenesis
• psoriasis
• treatment

• Humans
• Immunity, Innate
• Immunotherapy
• Neoplasms
• Receptors, Pattern Recognition
• Signal Transduction
• Tumor Microenvironment

Gastric cancer (GC) is a highly prevalent tumor type. The dysregulated expression of melanoma deficiency factor 2 (AIM2) has been observed in a range of tumor types. Herein, we explore the role of AIM2 in the regulation of GC progression.

Gastric cancer cells BGC-823 and MGC-803 in logarithmic growth phase were divided into blank group (control), Control group (NC) and SH-AIM2 group, respectively. Control group and SH-AIM2 group were transfected with AIM2 NC and SH-AIM2, respectively. Nude mice were divided into blank group (control) and SH-AIM2 group, and the treatment methods were the same as above. Differential AIM2 expression in GC tissues was assessed via bioinformatics analyses, after which western blotting was used for analyzing the AIM2 levels in tumor and paracancerous tissues from five stomach cancer patients. In addition, qPCR and protein imprinting were used to assess AIM2 expression levels in GC cells, and AIM2 knockdown was conducted in MGC-803 and BGC-823cells, after which colony formation and EdU incorporation assay were utilized to assess cell proliferation. The oncogenic role of AIM2 was then assessed in mice and validated through immunohistochemical analyses.

GC tissues and cell lines exhibited marked AIM2 overexpression. AIM2 knockdown significantly impaired GC cell proliferation and migration, as confirmed through in vitro assays. In vivo experiments showed that both the increment ability and invasion and migration ability of AIM2 knockdown group were significantly lower than that of control and NC the change of AIM2 protein level would affect the change of MAPK pathway related protein level.

AIM2 knockdown markedly suppresses the proliferation, migration, as well as invasion of GC cells via the inhibition of MAPK signaling, thereby slowing tumor progression. Overall, these results suggest that further analyses of AIM2 may offer clinically valuable insights that can aid in the treatment of human GC.

• AKT-mTOR
• Immunometabolism
• NLRP3/AIM2 inflammasomes
• NLRs
• STING
• innate sensors/receptors

• Autoimmune Diseases
• Humans
• Immunity, Innate
• Neoplasms
• Phosphatidylinositol 3-Kinases/metabolism
• Signal Transduction
• Toll-Like Receptors/metabolism

• P01 DK094779 NIDDK NIH HHS
• R56 AI029564 NIAID NIH HHS
• R01 AI029564 NIAID NIH HHS
• U19 AI067798 NIAID NIH HHS
• R35 CA232109 NCI NIH HHS
• R01 AI141333 NIAID NIH HHS
• U.S. Department of Health & Human Services | National Institutes of Health (NIH)

The innate immune system defenses against pathogen infections via patten-recognition receptors (PRRs). PRRs initiate immune responses by recognizing pathogen-associated molecular patterns (PAMPs), including peptidoglycan, lipopolysaccharide, and nucleic acids. Several nucleic acid sensors or families have been identified, such as RIG-I-like receptors (RLRs), Toll-like receptors (TLRs), cyclic GMP-AMP synthase (cGAS), and PYHIN family receptors. In recent years, the PYHIN family cytosolic DNA receptors have increased attention because of their important roles in initiating innate immune responses. The family members in humans include Absent in melanoma 2 (AIM2), IFN-γ inducible protein 16 (IFI16), interferon-inducible protein X (IFIX), and myeloid cell nuclear differentiation antigen (MNDA). The PYHIN family members are also identified in mice, including AIM2, p202, p203, p204, and p205. Herein, we summarize recent advances in understanding the activation and immune regulation mechanisms of the PYHIN family during microbial infection. Furthermore, structural characterizations of AIM2, IFI16, p202, and p204 provide more accurate insights into the signaling mechanisms of PYHIN family receptors. Overall, the molecular details will facilitate the development of reagents to defense against viral infections.

• National Natural Science Foundation of China

• AIM2
• autoimmune diseases
• cGAS-STING
• cancers

• Carcinoma, Non-Small-Cell Lung
• DNA-Binding Proteins
• Humans
• Lung Neoplasms
• Lupus Erythematosus, Systemic
• Melanoma/genetics

• 2020JJ2055 Hunan Outstanding Young Investigator
• 2019RS2012 Hunan Talent Young Investigator
• 81972943 National Natural Science Foundation of China
• 81830097 National Natural Science Foundation of China
• National Natural Science Foundation of China

A deficient mismatch repair system (dMMR) results in microsatellite instability (MSI). The MSI status of a tumor predicts the response to immune checkpoint inhibitors (ICI) that are now approved in patients with dMMR/MSI metastatic colorectal cancers. In addition to the mechanisms through which MSI can activate the immune system via particular neo-antigens, this review reports the clinical and pre-clinical strategies being developed in the case of resistance to ICI, including emerging therapies and new biomarkers.

A defect in the DNA repair system through a deficient mismatch repair system (dMMR) leads to microsatellite instability (MSI). Microsatellites are located in both coding and non-coding sequences and dMMR/MSI tumors are associated with a high mutation burden. Some of these mutations occur in coding sequences and lead to the production of neo-antigens able to trigger an anti-tumoral immune response. This explains why non-metastatic MSI tumors are associated with high immune infiltrates and good prognosis. Metastatic MSI tumors result from tumor escape to the immune system and are associated with poor prognosis and chemoresistance. Consequently, immune checkpoint inhibitors (ICI) are highly effective and have recently been approved in dMMR/MSI metastatic colorectal cancers (mCRC). Nevertheless, some patients with dMMR/MSI mCRC have primary or secondary resistance to ICI. This review details carcinogenesis and the mechanisms through which MSI can activate the immune system. After which, we discuss mechanistic hypotheses in an attempt to explain primary and secondary resistances to ICI and emerging strategies being developed to overcome this phenomenon by targeting other immune checkpoints or through vaccination and modification of microbiota.

• colorectal cancer
• deficient mismatch repair
• immune checkpoint inhibitor
• immunotherapy
• microbiota
• microsatellite instability

• antitumor immunity
• cancer
• genomic instability
• genomic stress

• BRAF-mutant
• absent in melanoma 2
• caspase-1
• colorectal cancer
• patient-derived organoids

• DNA sensing
• autophagy
• cGAS
• cell death
• infection
• inflammasome
• innate immunity
• interferon

The immune system has evolved to protect the host from the pathogens and allergens surrounding their environment. The immune system develops in such a way to recognize self and non-self and develops self-tolerance against self-proteins, nucleic acids, and other larger molecules. However, the broken immunological self-tolerance leads to the development of autoimmune or autoinflammatory diseases. Pattern-recognition receptors (PRRs) are expressed by immunological cells on their cell membrane and in the cytosol. Different Toll-like receptors (TLRs), Nod-like receptors (NLRs) and absent in melanoma-2 (AIM-2)-like receptors (ALRs) forming inflammasomes in the cytosol, RIG (retinoic acid-inducible gene)-1-like receptors (RLRs), and C-type lectin receptors (CLRs) are some of the PRRs. The DNA-sensing receptor cyclic GMP–AMP synthase (cGAS) is another PRR present in the cytosol and the nucleus. The present review describes the role of ALRs (AIM2), TLR9, and cGAS in recognizing the host cell DNA as a potent damage/danger-associated molecular pattern (DAMP), which moves out to the cytosol from its housing organelles (nucleus and mitochondria). The introduction opens with the concept that the immune system has evolved to recognize pathogens, the idea of horror autotoxicus, and its failure due to the emergence of autoimmune diseases (ADs), and the discovery of PRRs revolutionizing immunology. The second section describes the cGAS-STING signaling pathway mediated cytosolic self-DNA recognition, its evolution, characteristics of self-DNAs activating it, and its role in different inflammatory conditions. The third section describes the role of TLR9 in recognizing self-DNA in the endolysosomes during infections depending on the self-DNA characteristics and various inflammatory diseases. The fourth section discusses about AIM2 (an ALR), which also binds cytosolic self-DNA (with 80–300 base pairs or bp) that inhibits cGAS-STING-dependent type 1 IFN generation but induces inflammation and pyroptosis during different inflammatory conditions. Hence, this trinity of PRRs has evolved to recognize self-DNA as a potential DAMP and comes into action to guard the cellular galaxy. However, their dysregulation proves dangerous to the host and leads to several inflammatory conditions, including sterile-inflammatory conditions autoinflammatory and ADs.

• Toll-like receptor 9
• absent in melanoma-2
• absent in melanoma-2-like receptors
• autoimmunity
• cyclic GMP–AMP synthase
• inflammation
• stimulator of interferon genes

Inflammasomes are cytoplasmic inflammatory signaling protein complexes that detect microbial materials, sterile inflammatory insults, and certain host-derived elements. Inflammasomes, once activated, promote caspase-1–mediated maturation and secretion of pro-inflammatory cytokines, interleukin (IL)-1β and IL-18, leading to pyroptosis. Current advances in inflammasome research support their involvement in the development of chronic inflammatory disorders in contrast to their role in regulating innate immunity. Cannabis (marijuana) is a natural product obtained from the Cannabis sativa plant, and pharmacologically active ingredients of the plant are referred to as cannabinoids. Cannabinoids and cannabis extracts have recently emerged as promising novel drugs for chronic medical conditions. Growing evidence indicates the potent anti-inflammatory potential of cannabinoids, especially Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), and synthetic cannabinoids; however, the mechanisms remain unclear. Several attempts have been made to decipher the role of cannabinoids in modulating inflammasome signaling in the etiology of chronic inflammatory diseases. In this review, we discuss recently published evidence on the effect of cannabinoids on inflammasome signaling. We also discuss the contribution of various cannabinoids in human diseases concerning inflammasome regulation. Lastly, in the milieu of coronavirus disease-2019 (COVID-19) pandemic, we confer available evidence linking inflammasome activation to the pathophysiology of COVID-19 suggesting overall, the importance of cannabinoids as possible drugs to target inflammasome activation in or to support the treatment of a variety of human disorders including COVID-19.

• Delta-9 tetrahydrocannabinol
• cannabidiol
• cannabinoids
• inflammasome
• inflammasome signaling
• pro-inflammatory cytokines

• AIM2
• HCC
• NAFLD
• NASH
• absent in melanoma 2
• cirrhosis
• fibrosis
• hepatitis
• inflammasome
• liver disease

• Animals
• Carcinoma, Hepatocellular/pathology
• Cytokines/metabolism
• DNA-Binding Proteins/metabolism
• DNA-Binding Proteins/physiology
• Fatty Liver/pathology
• Hepatitis B/pathology
• Humans
• Inflammasomes/metabolism
• Inflammation/pathology
• Interleukin-18/metabolism
• Interleukin-1beta/metabolism
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/pathology
• Liver Diseases/metabolism
• Liver Diseases/physiopathology
• Liver Neoplasms/pathology
• Non-alcoholic Fatty Liver Disease/pathology
• Pyroptosis/physiology

DNA mismatch repair-deficient colorectal cancers (CRCs) accumulate numerous frameshift mutations at repetitive sequences recognized as microsatellite instability (MSI). When coding mononucleotide repeats (cMNRs) are affected, tumors accumulate frameshift mutations and premature termination codons (PTC) potentially leading to truncated proteins. Nonsense-mediated RNA decay (NMD) can degrade PTC-containing transcripts and protect from such faulty proteins. As it also regulates normal transcripts and cellular physiology, we tested whether NMD genes themselves are targets of MSI frameshift mutations. A high frequency of cMNR frameshift mutations in the UPF3A gene was found in MSI CRC cell lines (67.7%), MSI colorectal adenomas (55%) and carcinomas (63%). In normal colonic crypts, UPF3A expression was restricted to single chromogranin A-positive cells. SILAC-based proteomic analysis of KM12 CRC cells revealed UPF3A-dependent down-regulation of several enzymes involved in cholesterol biosynthesis. Furthermore, reconstituted UPF3A expression caused alterations of 85 phosphosites in 52 phosphoproteins. Most of them (38/52, 73%) reside in nuclear phosphoproteins involved in regulation of gene expression and RNA splicing. Since UPF3A mutations can modulate the (phospho)proteomic signature and expression of enzymes involved in cholesterol metabolism in CRC cells, UPF3A may influence other processes than NMD and loss of UPF3A expression might provide a growth advantage to MSI CRC cells.

• DNA mismatch repair
• MSI tumorigenesis
• UPF3A
• coding mononucleotide repeats
• nonsense-mediated RNA decay

• Cell Line, Tumor
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Frameshift Mutation
• Gene Expression Profiling
• Genomic Instability
• Humans
• Microsatellite Repeats
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Nonsense Mediated mRNA Decay
• Phosphoproteins/genetics
• Phosphoproteins/metabolism
• Proteomics
• RNA-Binding Proteins/genetics
• RNA-Binding Proteins/metabolism

• AIM2 inflammasome
• DNA binding
• Death domain
• HIN domain
• Helical filament
• Nucleated polymerization
• PYD

• AIM2 inflammasome
• DROSHA
• IPF
• miRNA

• Apoptosis
• Necroptosis
• Nucleic acid sensing
• Pyroptosis
• Type I interferon

• Cell Death/genetics
• DEAD Box Protein 58/chemistry
• DEAD Box Protein 58/genetics
• DNA-Binding Proteins/chemistry
• DNA-Binding Proteins/genetics
• Humans
• Immunity, Innate/genetics
• Interferon Type I/genetics
• Interleukin-1beta/genetics
• Nucleic Acids/chemistry
• Nucleic Acids/genetics
• Nucleotidyltransferases/chemistry
• Nucleotidyltransferases/genetics
• RNA-Binding Proteins/genetics
• Receptors, Immunologic

• 100954 Wellcome Trust
• MC_UU_00008/8 Medical Research Council
• 109024/Z/15/Z Wellcome Trust

• AIM2
• cell death
• gasdermin
• inflammasome
• pyroptosis

• AIM2
• Akt
• CRC
• EMT
• inflammasome

• AIM2
• HCC
• diethylnitrosamine
• inflammasome
• inflammation

• Antimicrobial response
• Host defence
• Inflammasome
• Innate immunity
• Microbial infection
• Nitric oxide

Absent in melanoma (AIM2) is a member of the interferon-inducible HIN-200 protein family and is recently recognized to play an important dual role in both innate immunity and tumor pathology. However, the role of AIM2 in the development of hepatocellular carcinoma (HCC) remains to be clarified. Here we showed that AIM2 expression was significantly decreased in liver cancer tissues, and loss of its expression was significantly correlated with more advanced tumor progression. Exogenous overexpression of AIM2 in HCC cells suppressed mammalian target of rapamycin (mTOR)-S6K1 pathway and further inhibited proliferation, colony formation and invasion of HCC cells. On the contrary, block of AIM2 in HCC cells induced (mTOR)-S6K1 pathway activation and thus promoted HCC progression. Treatment with mTOR pathway inhibitor rapamycin further verified its contribution to HCC progression in AIM2 absent HCC cells. Thus, these data suggested that AIM2 played a critical role as a tumor suppressor and might serve as a potential therapeutic target for future development of AIM2-based gene therapy for human liver cancer. This study also paves a new avenue to treat AIM2-deficient cancer by suppression of mTOR.

• absent in melanoma 2
• hepatocellular carcinoma
• inflammasome
• mammalian target of rapamycin
• tumor progression

• Cell proliferation
• Colitis
• Colorectal cancer
• Nucleic acid sensing pattern recognition receptors
• Type I interferon

• Animals
• Colitis/metabolism
• Colorectal Neoplasms/metabolism
• Humans
• Models, Biological
• Nucleic Acids/metabolism
• Receptors, Pattern Recognition/metabolism
• Signal Transduction

• Talents’ Start-up Fund of Gannan Medical University
• Natural Science Foundation of Jiangxi Province (CN)
• National Natural Science Foundation of China
• The Key Project from Department of Education of Jiangxi Province

• AIM2
• PI3K/Akt pathway
• apoptosis
• colorectal cancer

• Colitis
• Colorectal cancer
• Inflammasome
• Inflammation
• PYHIN-family proteins

• Animals
• Carcinogenesis/metabolism
• Carcinogenesis/pathology
• Cell Proliferation
• Colitis/pathology
• DNA-Binding Proteins/metabolism
• Humans
• Neoplasms/metabolism
• Neoplasms/pathology
• Protein Multimerization

• I01 BX001133 BLRD VA
• U.S. Department of Veterans Affairs

• AIM2 inflammasome
• Autoimmunity
• Bacterial/viral infection
• Cancer
• DNA sensing
• Gut microbiota

The absent in melanoma 2 (AIM2), a cytosolic dsDNA inflammasome, can be activated by viral DNA to trigger caspase-1. Its role in immunopathology of chronic hepatitis B and C virus (HBV, HCV) infection is still largely unclear. In this study, the expression AIM2, and its downstream cytokines, caspase-1, IL-18 and IL-1β, in liver tissue of patients with chronic hepatitis B and C (CHB, CHC) were investigated.

A total of 70 patients diagnosed with chronic hepatitis were enrolled, including 47 patients with CHB and 23 patients with CHC. A liver biopsy was taken from each patient, and immunohistochemistry was used to detect the expression of AIM2 and inflammatory factors caspase-1, IL-18, and IL-1β in the biopsy specimens. The relationship between AIM2 expression and these inflammatory factors was analyzed.

The expression of AIM2 in CHB patients (89.4 %) was significantly higher than in CHC patients (8.7 %), and among the CHB patients, the expression of AIM2 was significantly higher in the high HBV replication group (HBV DNA ≥ 1 × 10⁵copies/mL) than in the low HBV replication group (HBV DNA < 1 × 10⁵copies/mL). The expression of AIM2 was also correlated with HBV-associated inflammatory activity in CHB patients statistically. Additionally, AIM2 levels were positively correlated with the expression of caspase-1, IL-1β and IL-18 in CHB patients, which implied that the AIM2 expression is directly correlated with the inflammatory activity associated with CHB.

AIM2 upregulation may be a component of HBV immunopathology. The underlying mechanism and possible signal pathway warrant further study.

Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF) have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm² mucosa in the colorectum of Lynch syndrome patients) was significantly associated with patients’ age, but not with patients’ gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12). Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1) with 33%, followed by AIM2 (17%) and BAX (10%). Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients’ age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers.

• cancer prognosis
• inflammation
• interferon (IFN)
• tissue microarray
• tumor marker

Colorectal cancers (CRCs) with a high level of microsatellite instability (MSI-H) are clinicopathologically distinct tumors characterized by predominance in females, proximal colonic localization, poor differentiation, mucinous histology, tumor-infiltrating lymphocytes, a Crohn’s-like lymphoid reaction and a favorable prognosis. In terms of their molecular features, MSI-H CRCs are heterogeneous tumors associated with various genetic and epigenetic alterations, including DNA mismatch repair deficiency, target microsatellite mutations, BRAF mutations, a CpG island methylator phenotype-high (CIMP-H) status, and a low level of genomic hypomethylation. The molecular heterogeneity of MSI-H CRCs also depends on ethnic differences; for example, in Eastern Asian countries, relatively low frequencies of CIMP-H and BRAF mutations have been observed in MSI-H CRCs compared to Western countries. Although the prognostic features of MSI-H CRCs include a favorable survival of patients and low benefit of adjuvant chemotherapy, there may be prognostic differences based on the molecular heterogeneity of MSI-H CRCs. Here, we have reviewed and discussed the molecular and prognostic features of MSI-H CRCs, as well as several putative prognostic or predictive molecular markers, including HSP110 expression, beta2-microglobulin mutations, myosin 1a expression, CDX2/CK20 expression, SMAD4 expression, CIMP status and LINE-1 methylation levels.

• Colorectal cancer
• Microsatellite instability
• DNA mismatch repair
• DNA methylation
• CpG islands
• Prognosis
• Adjuvant chemotherapy

• CDX2 Transcription Factor
• Cell Differentiation
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• CpG Islands
• DNA Methylation
• DNA Repair
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Germ-Line Mutation
• Homeodomain Proteins/metabolism
• Humans
• Long Interspersed Nucleotide Elements/genetics
• Microsatellite Instability
• Microsatellite Repeats/genetics
• Mutation
• Phenotype
• Prognosis
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins B-raf/metabolism
• Proto-Oncogene Proteins p21(ras)
• Smad4 Protein/metabolism
• Treatment Outcome
• ras Proteins/metabolism

Despite improvements over the past two decades, the outcome for patients with advanced osteosarcoma remains poor. Targeted therapies have emerged as promising treatment options for various malignancies. However, effective targeted cancer therapies require the identification of key molecules in the pathogenesis of cancer. The aim of this study was to evaluate the value of the myeloid cell nuclear differentiation antigen (MNDA), a member of the interferon-inducible p200 (IFI-200) family, as a therapeutic target for osteosarcoma by analyzing the baseline expression of MNDA in human osteosarcoma cells and determining the effect of MNDA overexpression on the proliferation and apoptosis profiles and migration/invasion ability in osteosarcoma cells. To this end, MNDA mRNA abundance in wild-type sarcoma osteogenic (Saos-2) cells was analyzed using reverse transcription-polymerase chain reaction, proliferation/apoptosis profiles and migration/invasion capacity in Saos-2 cells overexpressing a green fluorescence protein (GFP)-human MNDA fusion protein. Saos-2 cells found to be overexpressing GFP alone were assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis and Matrigel Transwell migration assay. The results demonstrated that MNDA mRNA was significantly less abundant in wild-type Saos-2 cells compared with human monocyte-like U-937 cells and MNDA overexpression effectively inhibited proliferation, induced apoptosis and reduced migration/invasiveness in Saos-2 cells compared with GFP overexpression alone. Preliminary observations suggested that MNDA potentially serves as a novel therapeutic target for osteosarcoma.

• apoptosis
• invasion
• myeloid nuclear differentiation antigen
• osteosarcoma
• overexpression
• proliferation
• sarcoma osteogenic