RESUMEN
It has been certified that GABPB1-AS1 is aberrantly expressed and plays as a vital role in some kinds of cancers. However, its expression pattern and functions in non-small cell lung cancer (NSCLC) are still largely unknown. This study aims to assess GABPB1-AS1 expression and biological roles in NSCLC. The expression of GABPB1-AS1 was detected in NSCLC specimens and adjacent normal specimens. CCK8 and Transwell assays were performed to evaluate the effects of GABPB1-AS1 on NSCLC cell proliferation, migration and invasion. Bioinformatics tools and luciferase reporter assays were applied to predict and verify GABPB1-AS1's direct targets. The results revealed that GABPB1-AS1 is sharply reduced in NSCLC specimens and cell lines. CCK8 assays indicated that overexpression of GABPB1-AS1 dramatically reduced NSCLC cell growth, and Transwell assays proved that NSCLC cell migration and invasion were distinctly inhibited by GABPB1-AS1. Exploration of the mechanism uncovered that miRNA-566 (miR-566)/F-box protein 47 (FBXO47) is directly targeted by GABPB1-AS1 in NSCLC. The study demonstrated that GABPB1-AS1 inhibited NSCLC cell proliferation, migration and invasion by targeting miR-566/FBXO47.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Proteínas F-Box , Neoplasias Pulmonares , MicroARNs , Humanos , MicroARNs/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Línea Celular , Factor de Transcripción de la Proteína de Unión a GA , Factores de TranscripciónRESUMEN
Increasing evidence demonstrates that tRNA-derived fragments (tRFs) exert important effects and are dysregulated in various human cancer types. However, their roles in gastric cancer (GC) remain unknown. Here we identified the functional effects of tRF-3019a (derived from tRNA-Ala-AGC-1-1) in GC. We demonstrated that tRF-3019a was upregulated in GC tissues and cell lines. Phenotypic studies revealed that tRF-3019a overexpression enhances GC cell proliferation, migration and invasion. Conversely, tRF-3019a knockdown inhibits GC cell malignant activities. Mechanistic investigation implies that tRF-3019a directly regulates tumor suppressor gene FBXO47. Furthermore, tRF-3019a levels may discriminate GC tissues from nontumorous tissues. Taken together, our results reveal that tRF-3019a modulates GC cell proliferation, migration and invasion by targeting FBXO47, and it may serve as a potential diagnostic biomarker for GC.
Asunto(s)
ARN de Transferencia Aminoácido-Específico/genética , ARN de Transferencia/metabolismo , Neoplasias Gástricas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Secuencia de Bases , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Conformación de Ácido Nucleico , TransfecciónRESUMEN
Germ cells have the ability to differentiate into eggs and sperm and must determine their sexual fate. In vertebrates, the mechanism of commitment to oogenesis following the sexual fate decision in germ cells remains unknown. Forkhead-box protein L3 (foxl3) is a switch gene involved in the germline sexual fate decision in the teleost fish medaka (Oryzias latipes). Here, we show that foxl3 organizes two independent pathways of oogenesis regulated by REC8 meiotic recombination protein a (rec8a), a cohesin component, and F-box protein (FBP) 47 (fbxo47), a subunit of E3 ubiquitin ligase. In mutants of either gene, germ cells failed to undergo oogenesis but developed normally into sperm in testes. Disruption of rec8a resulted in arrest at a meiotic pachytenelike stage specifically in females, revealing a sexual difference in meiotic progression. Analyses of fbxo47 mutants showed that this gene regulates transcription factors that facilitate folliculogenesis: LIM homeobox 8 (lhx8b), factor in the germline α (figla), and newborn ovary homeobox (nobox). Interestingly, we found that the fbxo47 pathway ensures that germ cells do not deviate from an oogenic pathway until they reach diplotene stage. The mutant phenotypes together with the timing of their expression imply that germline feminization is established during early meiotic prophase I.
Asunto(s)
Proteínas de Peces/metabolismo , Células Germinativas/citología , Gónadas/embriología , Oogénesis , Oryzias/crecimiento & desarrollo , Folículo Ovárico/fisiología , Espermatozoides/fisiología , Animales , Femenino , Proteínas de Peces/genética , Regulación del Desarrollo de la Expresión Génica , Células Germinativas/fisiología , Gónadas/metabolismo , Masculino , Meiosis , Folículo Ovárico/citología , Procesos de Determinación del Sexo , Espermatogénesis , Espermatozoides/citologíaRESUMEN
In orange-spotted grouper, androgen can promote the development of testis and spermatogenesis, but the effect of androgen on testis development is unclear. Forkhead box L 3 (Foxl3) is important in the development of fish testis. Rec8 and fbxo47 are involved in meiosis, which impacts spermatogenesis. The present study investigated the plausible role of testis development through the Foxl3 transcriptional regulation of rec8 and fbxo47. The results of tissue distribution showed that rec8 and fbxo47 are highly expressed in gonad. In addition, the highest expression of foxl3, rec8, and fbxo47 was in the testis and intersex compared with the other stages of gonadal development, suggesting that foxl3, rec8, and fbxo47 are important in testis development. In addition, by using dual-luciferase assays, we found that the androgen can increase foxl3 promoter activity and Foxl3 can upregulate rec8 and fbxo47 promoter activity. Furthermore, the addition of ß-testosterone significantly increased foxl3, rec8, and fbxo47 promoter activity. Together, these results suggest that foxl3 plays a decisive role in testis development by regulating the expression of rec8 or fbxo47 and imply that AR-foxl3-rec8/fbxo47 affects the testis development pathway.