RESUMO
OBJECTIVES: lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) acts as an oncogene involved in papillary thyroid carcinoma (PTC) occurrence and progression. ABHD11-AS1 exerts biologic functions by some miRNAs and proteins to regulate multiple targets. Identification of novel mechanism of ABHD11-AS1 could be helpful in therapeutic targeting for PTC treatment. METHODS: Differentially expressed lncRNAs were selected from TCGA database. qRT-PCR analysis was applied to examine the expression of ABHD11-AS1 in PTC cell lines and tissues. The relationship of ABHD11-AS1 expression and clinicopathological features was analyzed by Kaplan-Meier analysis. Two PTC cell lines (TPC-1 and KTC-1) were transfected with pcDNA 3.1, pcDNA3.1-ABHD11-AS1, si-NC and si-ABHD11-AS1, respectively, to verify the ABHD11-AS1 oncogene-regulating capacity to promote tumor progression. The cell metastasis and proliferation had been evaluated both in vitro and in vivo. RESULTS: High expression of ABHD11-AS1 was found in PTC tissues (P < 0.01), which was significantly correlated with lymph node metastasis (P < 0.05). ABHD11-AS1 overexpression noticeably promoted cell proliferation, migration, and invasion capabilities, which were obviously decreased upon ABHD11-AS1 knockdown. ABHD11-AS1 positively regulated EGFR/EPS15L1 pathway, as EGFR, EPS15L1, STAT3, and p-STAT3 were activated. CONCLUSION: ABHD11-AS1 promotes tumor progression in PTC by regulating EPS15L1/EGFR pathway.
Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , RNA Antissenso/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Serina Proteases/genética , Serina Proteases/metabolismo , Transdução de Sinais/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
Grapevine downy mildew, caused by Plasmopara viticola, is a devastating disease that results in considerable economic losses as well as environmental damage through the repeated application of fungicides. The nucleotide-binding site leucine-rich repeat gene family functions in plant immunoactivity against various pathogens and pests. In this study, the 5' and 3' ends of the resistance gene homology fragment RGA5 were obtained by rapid amplification of cDNA ends. The 4282-base pair full-length cDNA was obtained using gene-specific primers, and the corresponding 1335-amino acid protein sequence contained characteristic nucleotide-binding site leucine-rich repeat domains of plant resistance proteins, including the toll-interleukin receptor type region. Expression of RGA5 during P. viticola infection and abiotic stress was investigated using quantitative real-time polymerase chain reaction. The results showed that treatment with P. viticola and 4 abiotic stimuli (salicyclic acid, methyl-jasmonate, abscisic acid, H2O2) significantly induced RGA5 within 12 days of inoculation. Therefore, RGA5 may play a critical role in protecting grapevines against P. viticola via signaling pathways involving these molecules.
Assuntos
Resistência à Doença/genética , Genes de Plantas , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Vitis/genética , Vitis/microbiologia , Sequência de Aminoácidos , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Peronospora/fisiologia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Estrutura Terciária de Proteína , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima/genéticaRESUMO
The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.
Assuntos
Animais , Masculino , Camundongos , Envelhecimento/metabolismo , Senescência Celular/fisiologia , Estradiol/metabolismo , Miócitos Cardíacos/fisiologia , Receptores Androgênicos/metabolismo , Testosterona/farmacologia , Envelhecimento/patologia , Biomarcadores/análise , /efeitos dos fármacos , Modelos Animais , Orquiectomia , Distribuição Aleatória , Proteína do Retinoblastoma/metabolismo , Encurtamento do Telômero/efeitos dos fármacos , Testosterona/deficiência , /metabolismoRESUMO
The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.