RESUMEN
We aimed to unveil the underlying pathogenic mechanisms of skin cancer in relation to metabolic factors and pathway mechanisms. This study utilized the TwoSample Mendelian randomization (MR) method to investigate the causal relationship between 1400 plasma metabolites and skin cancer. The primary method employed was the inverse variance weighting (IVW). Through IVW analysis, we found 105 plasma metabolites associated with Basal Cell Carcinoma (BCC), with the highest association observed for Prolylglycine levels (OR [95% CI]: 1.1902 [1.0274, 1.3788]). For Malignant Melanoma of Skin (MSS), 68 plasma metabolites were linked, with the highest causal relationship seen for 3-Hydroxybutyrate levels (OR [95% CI]: 1.0030 [1.0013, 1.0048]). Regarding actinic keratosis (AK), and the highest association observed for Hexadecadienoate (16:2n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.7125]). Glycerol to palmitoylcarnitine (16: n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.125]) were found to be significant for BCC and AK. Palmitoylcarnitine (C16) had the most positive causal effect for BCC (OR [95% CI]: 1.1777 [1.0493, 1.3218]), while 5-hydroxy-2-methylpyridine sulfate levels had the highest effect for AK (OR [95% CI]: 1.1788 [1.0295, 1.3498]). And 4-guanidinobutanoate levels had the largest positive causal effect (OR [95% CI]: 1.0857 [1.0417, 1.1317]) for BCC, and X-11880 levels for MSS (OR [95% CI]: 1.0013 [1.0000, 1.0025]). The study revealed a positive association between hereditary Glycerol to palmitoylcarnitine (C16) and 5-hydroxy-2-methylpyridine sulfate levels with the risk of developing BCC and AK. Additionally, 4-guanidinobutanoate levels and X 11880 levels were found to be positively associated with the risk of BCC and MMS.
Asunto(s)
Carcinoma Basocelular , Análisis de la Aleatorización Mendeliana , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/epidemiología , Carcinoma Basocelular/sangre , Carcinoma Basocelular/genética , Carcinoma Basocelular/epidemiología , Melanoma/sangre , Melanoma/genética , Melanoma/epidemiología , Queratosis Actínica/sangre , Queratosis Actínica/genética , Ácido 3-Hidroxibutírico/sangre , Predisposición Genética a la Enfermedad , Melanoma Cutáneo MalignoRESUMEN
OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with neurofibromatosis type I (NF1). METHODS: Target capture high-throughput sequencing and Sanger sequencing were carried out to detect the pathological variant in a NF1 patient and his parents. RESULTS: The proband and his similarly affected father have both harbored a novel nonsense variant of c.2511G>A (p.trp837x) in the NF1 gene. The same variant was not found in his mother and 200 healthy controls. CONCLUSION: The heterozygous nonsense variant of c.2511G>A (p.trp837x) of the NF1 gene probably underlay the pathogenesis of NF1 in this pedigree.
Asunto(s)
Neurofibromatosis 1 , China , Heterocigoto , Humanos , Mutación , Neurofibromatosis 1/genética , LinajeRESUMEN
Bladder cancer is one of the most frequently occurring malignant tumors in the urinary system. Sodium butyrate (NaB) is a histone deacetylase inhibitor and exerts remarkable antitumor effects in various cancer cells. MicroRNAs (miRNAs) and autophagy play crucial roles in cancer occurrence and development. In the present study, we evaluated the anticancer effects, including cell migration inhibition and the apoptotic effects of NaB in human bladder cancer cells. Furthermore, we found that NaB inhibited migration and induced AMPK/mTOR pathway-activated autophagy and reactive oxygen species (ROS) overproduction via the miR-139-5p/Bmi-1 axis. In addition, we found that ROS overproduction contributed to NaB-induced caspase-dependent apoptosis and autophagy. The interplay between autophagy and apoptosis in NaB treatment was clarified. Our findings provide a further understanding of EMT reversion, apoptosis and autophagy induced by antitumor drugs and a novel perspective and alternative strategy for bladder cancer chemotherapy.
Asunto(s)
Ácido Butírico/farmacología , Supervivencia Celular/fisiología , Potencial de la Membrana Mitocondrial/fisiología , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Cicatrización de Heridas/fisiología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Autofagia/efectos de los fármacos , Western Blotting , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Citometría de Flujo , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/genética , Ratones , Ratones Desnudos , Microscopía Electrónica de Transmisión , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To investigate the expression of long non-coding RNA-HOTAIR in prostate cancer cells and its effects on the growth and metastasis of the cells. METHODS: Using quantitative reverse-transcription PCR (qRT-PCR), we determined the relative expression of HOTAIR in the normal human prostate epithelial cell line RWPE-I and prostate cancer cell lines PC-3 and DU145. We detected the effects of HOTAIR on the cell cycle and invasiveness of prostate cancer cells by RNA interference, flow cytometry, and Transwell mitration assay. RESULTS: The expressions of HOTAIR in the PC3 and DU145 cells were increased 3.2 and 5.7 times, respectively, as compared with that in the normal RWPE-1 cells. After si-HOTAIR interference, the prostate cancer cells were arrested in the G2 phase and downregulated in the G1 phase. The invasive ability of the prostate cancer cells was evidently inhibited, with the inhibition rates of 32% and 44% of the PC3 cells and 43% and 34% of the DU145 cells for si-HOTAIR1 and si-HOTAIR2, respectively. CONCLUSION: IncRNA HOTAIR is highly expressed in prostate cancer, which is associated with the growth and invasiveness of prostate cancer cells. HOTAIR is potentially a novel marker for the diagnosis and prognosis of prostate cancer.
