RESUMO
Increasing evidence suggests that plasmacytoma variant translocation 1 (PVT1) plays a vital role in the development of multiple tumors including lung adenocarcinoma (LUAD). Eukaryotic initiation factor 4A-3 (EIF4A3) is considered a key factor in human cancers. However, the role and potential mechanism of PVT1 combined with EIF4A3 in LUAD remain unclear. This study investigated the effects and regulatory mechanisms of PVT1, EIF4A3, and circLMNB2 on the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of LUAD cells (H1299 and HCC827 cells) The expression level, diagnostic value and prognostic significance of PVT1, EIF4A3, and circLMNB2 were assessed, and enrichment analysis was performed using R package. Rescue experiments and a xenograft model were used to validate the PVT1/EIF4A3/circLMNB2 axis in LUAD. PVT1 and EIF4A3 were upregulated and indicated poor prognosis in LUAD. Knockdown of PVT1 and EIF4A3 suppressed LUAD cell proliferation, migration, invasion, and EMT. Mechanistically, PVT1 was stabilized by EIF4A3. PVT1 could recruit EIF4A3 to promote circLMNB2 expression. Rescue experiments indicated that circLMNB2 overexpression could reverse the reduced behavior caused by PVT1 or EIF4A3 knockdown. Enrichment analysis showed that PVT1/EIF4A3/circLMNB2 may regulate LUAD development by participating in ribosome biogenesis and spliceosome formation. Our findings demonstrate that PVT1/EIF4A3/circLMNB2 enhances the malignant behaviors of LUAD cells, providing a novel perspective for the clinical treatment of LUAD.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Fator de Iniciação 3 em Eucariotos/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , RNA Circular , RNA Longo não CodificanteRESUMO
OBJECTIVE: To observe the effect of compound of gardenia oil and jujube seed oil learning and memory in ovariectomized rats and its mechanism. METHODS: Animals were randomly divided into six groups: sham group, model group, estrogen group, low dose group, middle dose group and high dose group. The ovariectomized rat models were established by resection of the lateral ovaries. The effect of compound of gardenia oil and jujube seed oil on learning and memory in ovariectomized rats was observed by means of Morris water maze. Acetylcholinesterase (AchE) and nitric oxide synthase (NOS) activities in rat brain were determined. RESULTS: The compound of gardenia oil and jujube seed oil could shorten the incubation period of appearance in castration rats and increase the number passing through Yuan Ping table in ovariectomized rats. As the training time extended, the incubation period of appearance was gradually shortened. The compound of gardenia oil and jujube seed oil could increase NOS activity, and decrease AChE activity in brain of ovariectomized rats. CONCLUSION: The compound of jujube seed oil and gardenia oil could promote the learning and memory in ovariectomized rats. This effect may be related with the increase in activities of NOS, AchE in rat brain.