RESUMO
Current research has shown that inhibiting deoxythymidylate kinase (DTYMK) can significantly reduce development of lung cancer without liver kinase B1. However, its underlying regulatory mechanism is still unclear. We therefore aimed to investigate whether DTYMK inhibitors could suppress lung adenocarcinoma (LUAD) progression. In this study, human tissues, A549 cells, and xenograft tumors were used to explore the regulation and mechanism of DTYMK on LUAD cell proliferation and migration. Meanwhile, YMU1 (a DTYMK inhibitor) was applied to A549 cells and xenograft tumors to investigate its potential as a drug for LUAD. DTYMK was overexpressed in LUAD tissues and correlated with tumor stage. Knockdown of DTYMK suppressed cell viability, migration, and invasion. In addition, the activation of signal transducers and activators of transcription 3 (STAT3) was repressed upon DTYMK inhibition. YMU1 showed the same effect as DTYMK knockdown in vivo and in vitro. DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may have the potential to inhibit the development of LUAD.NEW & NOTEWORTHY DTYMK plays an important role in progression of LUAD through the STAT3 signaling pathway. YMU1 may serve as a novel drug to suppress the development of LUAD.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Timidina Monofosfato/farmacologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Transdução de Sinais , Pulmão/patologia , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologiaRESUMO
Rab-interacting lysosomal protein (RILP) has been suggested to perform as a tumor suppressor in breast and prostate cancer cell lines. However, its expression profile and functional role in lung cancer have never been investigated. We applied the well-established cancer genomic database-The Cancer Genome Atlas to compare the RILP expression and methylation between lung cancer tissues and normal tissues. The potential correlation of RILP with clinical characteristics of lung cancer patients (e.g., stages, smoking, TP53, and methylation) was also be explored. Our results showed that the downregulation of RILP and upregulation of RILP methylation were identified in lung cancer tissues compared to normal healthy tissues. Downregulation of RILP was positively associated with lung cancer later stage (N3), smoking history, TP53 mutation, and poor prognosis, as well as inversely correlated with DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression. Demethylation treatment enhanced RILP expression in lung cancer cells, suggesting hypermethylation is responsible for RILP silencing in lung cancer. We further found that RILP depletion promoted lung cancer cell proliferation, migration, and invasion. We concluded that RILP acts as a tumor suppressor in lung cancer cells. Our results provided the theoretical basis for developing RILP-targeting or demethylating agents for lung cancer treatment.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células Escamosas/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Metilação de DNA , Neoplasias Pulmonares/genética , Proteínas Supressoras de Tumor/metabolismo , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Biologia Computacional/métodos , DNA (Citosina-5-)-Metiltransferase 1/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Taxa de Sobrevida , Proteínas Supressoras de Tumor/genéticaRESUMO
In this study, we report the use of transareolar uniportal video-assisted thoracoscopic surgery (VATS) in thoracic surgery for the treatment of male patients with peripheral pulmonary nodules. From February 2014 to September 2018, 46 male patients with small PPNs underwent VATS, of whom 41 underwent unilateral VATS, and five underwent bilateral VATS. All procedures were successfully performed. Patients received 1 year of outpatient follow-up postoperatively. The data indicated that the average operation times were 32.7 min (unilateral) and 58.6 min (bilateral). The mean length of the incision was 2.7 ± 0.3 cm, with a mean cosmetic score of 3.2 ± 0.7 at the time of discharge. All patients rapidly recovered consciousness postoperatively. The length of postoperative hospitalization (LOH) was 3.4 ± 1.4 days. There was no obvious surgical scarring on the chest wall, and no patients complained of postoperative pain at 6 months postoperatively. No recurrence or metastasis was found during the 1-year follow-up. Transareolar uniportal VATS for peripheral pulmonary nodules resulted in good cosmetic outcomes and high patient satisfaction. Transareolar uniportal VATS is a safe and effective therapeutic procedure for male patients with small PPNs and especially produces good cosmetic outcomes.
Assuntos
Neoplasias Pulmonares , Cirurgia Torácica , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Estudos Retrospectivos , Cirurgia Torácica VídeoassistidaRESUMO
Lung cancer is one of the most common malignant tumors. It is clinically divided into two types: small cell lung cancer and non-small cell lung cancer. Populus simonii distributed in East Asia region including China used as traditional medicine, which is an important medicinal plant for anti-lung cancer activity. The complete chloroplast genome sequence of P. simonii was characterized from Illumina pair-end sequencing. The chloroplast genome of P. simonii was 156,559 bp in length, containing a large single-copy region (LSC) of 84,825 bp, a small single-copy region (SSC) of 47,561 bp, and two inverted repeat (IR) regions of 16,494 bp. The overall GC content is 36.70%, while the corresponding values of the LSC, SSC, and IR regions are 34.5%, 30.0%, and 42.0%, respectively. The genome contains 131 complete genes, including 86 protein-coding genes (68 protein-coding gene species), 37 tRNA genes (29 tRNA species), and 8 rRNA genes (4 rRNA species). The neighbour-joining phylogenetic analysis showed that P. simonii and P. qamdoensis clustered together as sisters to other Populus species.