RESUMO
OBJECTIVES: Malignant melanoma (MM) is an invasive tumor that poses a threat to patient health. Circular RNAs (circRNAs) are important regulators of MM carcinogenesis. In this study, we investigated the expression characteristics and biological functions of, and mechanism underlying, circ_0119872 expression in MM. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to examine the circ_0119872, microRNA (miR)-582-3p, and E2F transcription factor 3 (E2F3) mRNA expression levels in MM tissues and cell lines. Western blotting was performed to quantify E2F3 protein expression. MM cells with circ_0119872 knockdown were established, and cell counting kit 8 (CCK-8) and transwell assays were utilized to examine the function of circ_0119872 and its effects on the malignant characteristics of MM cells. The MiRDB and TargetScan databases were used to predict the target genes of miR-582-3p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to explore the biological functions of the target genes of miR-582-3p. Additionally, a dual-luciferase reporter gene experiment was performed to verify the targeting relationship between circ_0119872 and miR-582-3p as well as that between miR-582-3p and E2F3. RESULTS: Circ_0119872 was remarkably upregulated in MM tissues and cell lines. Circ_0119872 knockdown suppressed the cell proliferation and metastasis In addition, miR-582-3p was identified as a downstream target of circ_0119872. The target genes of miR-193a-3p are involved in melanogenesis and cancer-related signaling pathways. Mechanistically, circ_0119872 facilitated MM progression by adsorbing miR-582-3p and upregulating E2F3 expression. CONCLUSION: Circ_0119872 is an oncogenic circRNA that participates in the promotion of MM progression by regulating the miR-582-3p/E2F3 axis.
Assuntos
Melanoma , MicroRNAs , Linhagem Celular Tumoral , Fatores de Transcrição E2F , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/genética , MicroRNAs/genéticaRESUMO
OBJECTIVES: Malignant melanoma (MM) is an invasive tumor that poses a threat to patient health. Circular RNAs (circRNAs) are important regulators of MM carcinogenesis. In this study, we investigated the expression characteristics and biological functions of, and mechanism underlying, circ_0119872 expression in MM. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to examine the circ_0119872, microRNA (miR)-582-3p, and E2F transcription factor 3 (E2F3) mRNA expression levels in MM tissues and cell lines. Western blotting was performed to quantify E2F3 protein expression. MM cells with circ_0119872 knockdown were established, and cell counting kit 8 (CCK-8) and transwell assays were utilized to examine the function of circ_0119872 and its effects on the malignant characteristics of MM cells. The MiRDB and TargetScan databases were used to predict the target genes of miR-582-3p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to explore the biological functions of the target genes of miR-582-3p. Additionally, a dual-luciferase reporter gene experiment was performed to verify the targeting relationship between circ_0119872 and miR-582-3p as well as that between miR-582-3p and E2F3. RESULTS: Circ_0119872 was remarkably upregulated in MM tissues and cell lines. Circ_0119872 knockdown suppressed the cell proliferation and metastasis In addition, miR-582-3p was identified as a downstream target of circ_0119872. The target genes of miR-193a-3p are involved in melanogenesis and cancer-related signaling pathways. Mechanistically, circ_0119872 facilitated MM progression by adsorbing miR-582-3p and upregulating E2F3 expression. CONCLUSION: Circ_0119872 is an oncogenic circRNA that participates in the promotion of MM progression by regulating the miR-582-3p/E2F3 axis.
Assuntos
Humanos , MicroRNAs/genética , Melanoma/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Fatores de Transcrição E2FAssuntos
Povo Asiático/genética , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Esclerose Tuberosa/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Sequência de Bases , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 do Complexo Esclerose Tuberosa , Adulto JovemRESUMO
We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10(-14), OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10(-11), OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-κB pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.
