Purpose: Lung adenocarcinoma (LUAD) is a main subtype of lung cancer, which is the leading cause of cancer-related deaths. The five-year survival rates of lung cancer patients are still comparatively low. Therefore, potential therapeutic targets are urgently needed to improve the survival of lung cancer patients. In this study, we identified FAM111B as an oncogene and potential therapeutic target for LUAD. Methods: The TCGA database and tissue microarray analysis were used to compare the expression of FAM111B in tumor tissue and normal tissues and evaluate the relationship between FAM111B expression and clinical survival. FAM111B was knocked down and overexpressed to observe whether FAM111B could affect the proliferation, migration, cell cycle, and apoptosis of LUAD cells in vivo and in vitro. Results: FAM111B was highly expressed in tumor tissues compared with normal tissues ( P <0.01). LUAD patients with hyper-expression of FAM111B had a lower recurrence-free survival ( P <0.01) and shorter overall survival ( P <0.01). Knocking down FAM111B inhibited cell proliferation, migration and invasion in vitro and tumor growth in vivo. Silencing FAM111B could arrest LUAD cells at G2/M phase and increase apoptosis. Overexpression of FAM111B promoted the growth of lung cancer cells. FAM111B was identified as a direct target of p53 in existing researches by chip-seq analysis. Bioinformatics analysis predicted that FAM111B could directly bind to BAG3 (BCL2 associated athanogene 3). When FAM111B was down-regulated, both expression of BAG 3 and BCL2 were significantly reduced, whereas decreasing the expression of BAG3 had no effect on FAM111B. Conclusions: Our study indicated that FAM111B might be an oncogene and potential therapeutic target in LUAD which could be involved in the regulation of tumor cells by p53 signaling pathway and play an important role in the process of cell cycle and apoptosis by influencing the expression of BAG3 and BCL2.
These findings suggest that miR-221 is a novel prognostic indicator in gastric cancer and may be a potential target for diagnosis and gene therapy.
SUMMARY The aims of this pilot study are to evaluate the feasibility, safety, and effectiveness of conducting an enhanced nutritional support pathway including extended preoperative nutritional support and one month home enteral nutrition (HEN) for patients who underwent enhanced recovery after esophagectomy. We implemented extended preoperative nutritional support and one month HEN after discharge for patients randomized into an enhanced nutrition group and implemented standard nutritional support for patients randomized into a conventional nutrition group. Except the nutritional support program, both group patients underwent the same standardized enhanced recovery after surgery programs of esophagectomy based on published guidelines. Patients were assessed at preoperative day, postoperative day 7 (POD7), and POD30 for perioperative outcomes and nutritional status. To facilitate the determination of an effect size for subsequent appropriately powered randomized clinical trials and assess the effectiveness, the primary outcome we chose was the weight change before and after esophagectomy. Other outcomes including body mass index (BMI), lean body mass (LBM), appendicular skeletal muscle mass index (ASMI), nutrition-related complications, and quality of life (QoL) were also analyzed. The intention-to-treat analysis of the 50 randomized patients showed that there was no significant difference in baseline characteristics. The weight (−2.03 ± 2.28 kg vs. −4.05 ± 3.13 kg, P = 0.012), BMI (−0.73 ± 0.79 kg/m2 vs. −1.48 ± 1.11 kg/m2, P = 0.008), and ASMI (−1.10 ± 0.37 kg/m2 vs. −1.60 ± 0.66 kg/m2, P = 0.010) loss of patients in the enhanced nutrition group were obviously decreased compared to the conventional nutrition group at POD30. In particular, LBM (48.90 ± 9.69 kg vs. 41.96 ± 9.37 kg, p = 0.031) and ASMI (7.56 ± 1.07 kg/m2 vs. 6.50 ± 0.97 kg/m2, P = 0.003) in the enhanced nutrition group were significantly higher compared to the conventional nutrition group at POD30, despite no significant change between pre- and postoperation. In addition, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 scores revealed that enhanced nutritional support improved the QoL of patients in physical function (75.13 ± 9.72 vs. 68.33 ± 7.68, P = 0.009) and fatigue symptom (42.27 ± 9.93 vs. 49.07 ± 11.33, P = 0.028) compared to conventional nutritional support. This pilot study demonstrated that an enhanced nutritional support pathway including extended preoperative nutritional support and HEN was feasible, safe, and might be beneficial to patients who underwent enhanced recovery after esophagectomy. An appropriately powered trial is warranted to confirm the efficacy of this approach.
Background: The homeodomain transcription factor, PITX2 is associated with tumorigenesis of multiple cancers. In this research, we aimed to study the expression, function and mechanism of PITX2 in lung adenocarcinoma (LUAD). Methods: The TCGA dataset was used to analyze the expression and clinical significance of PITX2 in LUAD. The expression of PITX2 in tumor samples and LUAD cell lines was examined by quantitative real-time PCR (qRT-PCR) and western blotting. Small interfering RNAs (siRNAs) were constructed to knockdown PITX2 and to determine the physiological function of PITX2 in vitro. Xenograft model was used to confirm the role of PITX2 in vivo. Results: PITX2 was overexpressed in LUAD and patients with high level of PITX2 had a worse overall survival and an advanced clinical stage. Knockdown of PITX2 inhibited cell proliferation, migration and invasion of LUAD cells. Further study revealed that the oncogenic role of PITX2 was dependent on activating Wnt/β-catenin signaling pathway, especially by transcriptionally regulating the Wnt gene family member, WNT3A. Lastly, we identified miR-140-5p as a negative mediator of PITX2 by binding its 3′UTR and ectopic expression of miR-140-5p inhibited progression of LUAD cells via suppressing the expression of PITX2. Conclusions: Up-regulation of PITX2 acts as an oncogene in LUAD by activating Wnt/β-catenin signaling pathway, suggesting that PITX2 may serve as a novel diagnostic and prognostic biomarker in LUAD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.