MicroRNA­373­3p inhibits the proliferation and invasion of non­small­cell lung cancer cells by targeting the GAB2/PI3K/AKT pathway.

MicroRNAs (miRNAs) were previously demonstrated to be involved in the pathogenesis of non-small-cell lung cancer (NSCLC); however, the roles of certain miRNAs in NSCLC remain to be elucidated. The present study aimed to investigate the functions of screened miRNAs in NSCLC and the potential mechanisms. First, expression profiles of miRNAs were downloaded from the Gene Expression Omnibus (dataset no. GSE29248) and the differentially expressed miRNAs were analyzed by bioinformatics methods. Reverse transcription-quantitative PCR was used to validate the differential expression of miR-373 in clinical samples. The association between miR-373 expression levels and clinicopathological characteristics was also investigated. To further examine how miR-373 mediates the emergence of NSCLC, western blot, Cell Counting Kit-8, cell invasion and wound-healing assays, as well as apoptosis detection and a luciferase assay were used. The results indicated significant downregulation of miR-373 in NSCLC tissues and its low expression was closely associated with the degree of differentiation, clinical stage and tumor size, and was indicative of an unfavorable prognosis for patients with NSCLC. A functional study indicated that overexpression of miR-373 inhibited the proliferation, promoted apoptosis, and suppressed invasion and migration of NSCLC cells. Bioinformatics prediction and functional assays suggested that Grb-associated binding protein 2 (GAB2) was a direct target of miR-373. In addition, GAB2 was found to be significantly upregulated in NSCLC tissues, and clinically, miR-373 was negatively associated with GAB2. Furthermore, overexpression of GAB2 blocked the tumor suppressive effects of miR-373 on NSCLC cells. Mechanistically, miR-373 mimics were able to reduce the expression of GAB2 and subsequently decrease the phosphorylation level of AKT and mTOR protein. The present results indicate that miR-373 exerts its anti-tumor effects in NSCLC cells by targeting the GAB2/PI3K/AKT pathway, suggesting that miR-373 may be a potential therapeutic target in NSCLC.

IGF2BP3 aggravates lung adenocarcinoma progression by modulation of PI3K/AKT signaling pathway.

OBJECTIVES: The tumor-promoting function of IGF2BP3 has been reported in several cancers. The present study aimed to explore the function and molecular mechanisms of IGF2BP3 are elusive in lung adenocarcinoma (LUAD). METHODS: IGF2BP3 expression in LUAD and its prognostic value were estimated by bioinformatics. RT-qPCR was employed to detect the expression of IGF2BP3 and confirm the transfection efficiency following the knockdown or overexpression of IGF2BP3. Functional assays, including CCK-8, TUNEL, and Transwell assays, were used to determine the role of IGF2BP3 in tumor cell viability, apoptosis, migration and invasion. Gene Set Enrichment Analysis (GSEA) was used to identify signaling pathways related to IGF2BP3 expression. The effects of IGF2BP3 on the PI3K/AKT pathway were detected by western blotting. RESULTS: In this study, we found that IGF2BP3 was overexpressed in LUAD, and patients with high IGF2BP3 levels had a lower probability of overall survival. Moreover, ectopic expression of IGF2BP3 enhanced cell viability and metastasis, and reduced apoptosis. Conversely, IGF2BP3 silencing reduced the viability, migration, and invasion while enhancing the apoptosis of LUAD cells. In addition, it was disclosed that overexpression of IGF2BP3 could activate PI3K/AKT signaling in LAUD, while silencing of IGF2BP3 deactivated this pathway. Moreover, 740Y-P (PI3K agonist) reversed the inhibitory effects on cell viability and metastasis, and the promotion effect on metastasis caused by IGF2BP3 silencing. CONCLUSION: Our findings demonstrated that IGF2BP3 contributed to the tumorigenesis of LUAD by activating the PI3K/AKT signaling.

The short-term outcomes of nonintubated anesthesia compared with intubated anesthesia in single-port video-assisted lung surgery in enhanced recovery after thoracic surgery: results from a single-center retrospective study.

Background: Nonintubated anesthesia avoids invasive tracheal intubation operations and reduces trauma. in addition, it has advantages in lung surgery in some patients with poor lung function, in line with the concept of rapid recovery. However, few studies have discussed the clinical significance of Enhanced recovery after surgery (ERAS) combined with nonintubated anesthesia in single-port video-assisted thoracoscopic surgery (VATS). We conducted a retrospective study to examine the safety and availability of nonintubated anesthesia single-port video-assisted lung surgery (NI-SP-VALS) combined with ERAS programs in patients. Methods: This was a single-center retrospective study. All patients were preoperatively diagnosed with lung nodules and underwent NI-SP-VALS or intubated anesthesia SP-VALS (I-SP-VALS) combined with ERAS programs between July 2021 and March 2022. Short-term postoperative outcomes were compared in 2 cohorts. Results: In total, 272 patients were included. Among them, 91 patients received NI-SP-VALS combined with ERAS programs (observation group), and 181 underwent intubation anesthesia (control group). Baseline data were statistically different between the two groups, and 1:1 propensity score matching (PSM) matching was used. A total of 73 patients remained in each group after PSM, and baseline characteristics were not significantly different between the 2 cohorts. The time of hospital stay [4.00 (4.00-5.00) vs. 44.50 (0.00-5.75) d; P=0.029] and catheter stay [0.50 (0.20-2.00) vs. 2.00 (2.00-2.00) d; P<0.001] were significantly shorter, the white blood cell count (WBC) [9.45 (8.08-11.30) vs. 11 (8.50-12.80)/L; P=0.009] and the lowest SpO2 in operation [96.00 (94.00-97.50) vs. 97.00 (95.00-98.50); P=0.035] were also lower in the nonintubated group than those of the intubated group. No differences were observed in variables of intraoperation, other routine blood indexes, postoperative drainage, postoperative medicine use, postoperative symptoms, complications, hospitalization expenses, postoperative follow-up index, or self-assessment of anxiety. Conclusions: The data after PSM shows that compared with intubated anesthesia, NI-SP-VALS combined with ERAS programs is safe and effective. Nonintubated anesthesia promotes rapid recovery of patients and reduces postoperative inflammatory reactions. Hence, nonintubated anesthesia may conform to the idea of ERAS and has application value in thoracic surgery.

PP4C facilitates lung cancer proliferation and inhibits apoptosis via activating MAPK/ERK pathway.

PURPOSE: Protein phosphatase 4 catalytic subunit (PP4C) has been shown to play crucial regulatory roles in biological process and is frequently upregulated in cancer such as breast and colorectal carcinoma. However, the function and potential molecular mechanism of PP4C in lung cancer remains unclear. METHODS: Bioinformatic analysis was used to detect the expression level and prognosis of patients. Western blot, quantitative real-time PCR (qRT-PCR), CCK8, 5-Ethynyl-2'-deoxyuridine (Edu) proliferation assay and flow cytometric were used to explore the function in lung cancer cells. RESULTS: In this study, we found that PP4C was upregulated in lung cancer tissues as compared with that in normal lung tissues. Furthermore, patients with high expression level of PP4C were correlated with a poor prognosis in lung cancer patients. In vitro, CCK8, Edu proliferation assays and flow cytometry analysis showed that PP4C could promote lung cancer cell growth and inhibit apoptosis. Mechanistic investigations revealed that PP4C may interact with PP4R1 and promote ERK activation. Additionally, PP4C depletion resulted in lower tumor growth in vivo. CONCLUSIONS: Taken together, these data showed the oncogenic of PP4C in NSCLC tumorigenesis and provide a new insight of PP4C in the progression of NSCLC.

Prognostic significance and biological function of Lamina-associated polypeptide 2 in non-small-cell lung cancer.

Purpose: Lamina-associated polypeptide 2 (LAP2; encoded by TMPO), is a nuclear protein that may affect chromatin regulation and gene expression through dynamically binding to nuclear lamin. TMPO (LAP2) plays dual roles of either suppressing or promoting proliferation of cells, depending on the status of the cell. It has been reported that TMPO is up-regulated in various cancer types. However, its function in lung cancer has not been studied yet. Materials and methods: A series of clinical microarray datasets for lung cancer were investigated to demonstrate the expression of TMPO. The transcription of TMPO gene in human lung cancer was analyzed using Oncomine platform (www.oncomine.org) according to the standardized procedures described previously. Four separate datasets (Hou Lung, Okayama Lung, Beer Lung, and Garber Lung) were analyzed. Results: Here, we show that TMPO is over-expressed in lung cancer tissues, and that a high level of TMPO indicates a poor prognosis in lung cancer patients. Knockdown of TMPO in lung cancer cells inhibits cell proliferation and induces apoptosis. Also, down-regulation of TMPO leads to an impaired metastatic ability of tumor cells. A nude mice tumor model show that knockdown of TMPO suppresses tumor formation in vivo. Conclusion: Collectively, this study suggests TMPO as an oncogene and a novel prognostic gene in lung cancer.

Loss of asparagine synthetase suppresses the growth of human lung cancer cells by arresting cell cycle at G0/G1 phase.

The aim of this research is to determine the role of human asparagine synthetase (ASNS) in human lung cancer. In the present study, immunohistochemical staining and the Oncomine database mining showed that the expression of ASNS gene was higher in lung cancer tissues than that in the normal tissues by. In addition, western blot assay showed that ASNS was elevated in lung cancer A549 and 95D cell lines as compared with that in H1299 and H460 cells. Therefore, A549 and 95D cells were chosen for subsequent MTT and colony formation assay. It was found that knockdown of ASNS inhibited the growth and colony formation abilities of A549 and 95D cells. Flow cytometry showed that ASNS silencing arrested cell cycle progression at G0/G1 phase in A549 cells, probably through regulating the expression of cell cycle molecules such as CDK2 and Cyclin E1 as shown by quantitative real-time PCR. Taken together, our study indicates that ASNS may be an important target for lung cancer diagnosis and treatment.