Background Eukaryotic protein translation elongation factor 1α2 ( EEF1A2 ) is an oncogene that promotes the progression of breast and pancreatic cancer. In this study, we aimed to elucidate the oncogenic function of EEF1A2 in the metastasis of lung adenocarcinoma (LUAD). Methods Immunohistochemistry and western blot were used to study EEF1A2 expression levels in LUAD tissues and cells, respectively. The role of EEF1A2 in LUAD progression were investigated in vitro and in vivo. We identified potential EEF1A2-binding proteins by liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. Protein–protein interactions were determined by immunofluorescence and co-immunoprecipitation ( Co -IP). Results In this study, we report that EEF1A2 mediates the epithelial–mesenchymal transformation (EMT), to promote the metastasis of LUAD cells in vitro and in vivo. Moreover, EEF1A2 interacts with HSP90AB1 to increase TGFβ Receptor (TβR)-I, and TβRII expression, followed by enhanced SMAD3 and pSMAD3 expression and nuclear localisation, which promotes the EMT of LUAD cells. Overexpression of EEF1A2 in cancer tissues is associated with poor prognosis and short survival of patients with LUAD. Conclusions These findings underscore the molecular functions of EEF1A2 in LUAD metastasis and indicate that EEF1A2 represents a promising target in the treatment of aggressive LUAD.

Metabolic abnormalities are one of the essential features of tumors. Increasingly more studies have shown that lovastatin, a lipid-reducing drug, has visible inhibitory effects on tumors, but it has not been reported in nasopharyngeal carcinoma. In this paper, we explored the effects of lovastatin on the growth of nasopharyngeal carcinoma cells and its possible molecular mechanisms. After treating nasopharyngeal carcinoma cells with different concentrations of lovastatin, we found that lovastatin can inhibit the growth of nasopharyngeal carcinoma in a time- and dose-dependent manner. To explore the molecular mechanism of how lovastatin inhibits the growth of nasopharyngeal carcinoma, we examined the proteome of nasopharyngeal carcinoma cells treated at different time points using an LC/MS whole-proteomic strategy. The molecular network of differentially expressed proteins was constructed using IPA software. It was found that lovastatin inhibited the growth of nasopharyngeal carcinoma cells mainly by affecting the EIF2 and the mTOR pathways, which regulate cell metabolism and apoptosis. The results of this study provide a robust basis for further research on the molecular mechanism of lovastatin's inhibition of nasopharyngeal carcinoma cells and provide a reference for the clinical use of lovastatin in the treatment of nasopharyngeal carcinoma.

Long noncoding RNAs (lncRNAs) play an important role in lung adenocarcinoma (LUAD) metastasis. Here, we found that lncRNA chromatin-associated RNA 10 (CAR10) was upregulated in the tumor tissue of patients with LUAD and enhanced tumor metastasis in vitro and in vivo. Mechanistically, CAR10 induced epithelial-to-mesenchymal transition (EMT) by directly binding with miR-30 and miR-203 and then regulating the expression of SNAI1 and SNAI2. CAR10 overexpression was positively correlated with a poor prognosis in LUAD patients, whereas overexpression of both CAR10 and SNAI was correlated with even worse clinical outcomes. In conclusion, the CAR10/miR-30/203/SNAI axis is a novel and potential therapeutic target for LUAD.

Introduction: Transforming growth factor-beta (TGFβ) signaling plays a vital role in lung adenocarcinoma (LUAD) progression. However, the involvement of TGFβ-regulated long non-coding RNAs (lncRNAs) in metastasis of LUAD remains poorly understood. Methods: We performed bioinformatic analyses to identify putative lncRNAs regulated by TGF-β/SMAD3 and validated the results by quantitative PCR in LUAD cells. We performed luciferase reporter and chromatin immunoprecipitation assays to demonstrate the transcriptional regulation of the lncRNA histocompatibility leukocyte antigen complex P5 (HCP5) we decided to focus on. Stable HCP5 knockdown and HCP5-overexpressing A549 cell variants were generated respectively, to study HCP5 function and understand its mechanism of action. We also confirmed our findings in mouse xenografts and metastasis models. We analyzed the correlation between the level of lncRNA expression with EGFR, KRAS mutations, smoke state and prognostic of LUAD patients. Results: We found that the lncRNA HCP5 is induced by TGFβ and transcriptionally regulated by SMAD3, which promotes LUAD tumor growth and metastasis. Moreover, HCP5 is overexpressed in tumor tissues of patients with LUAD, specifically in patients with EGFR and KRAS mutations and current smoker. HCP5 high expression level is positively correlated with poor prognosis of patients with LUAD. Finally, we demonstrated that upregulation of HCP5 increases the expression of Snail and Slug by sponging the microRNA-203 (miR-203) and promoting epithelial-mesenchymal transition (EMT) in LUAD cells. Conclusions: Our work demonstrates that the lncRNA HCP5 is transcriptionally regulated by SMAD3 and acts as a new regulator in the TGFβ/SMAD signaling pathway. Therefore, HCP5 can serve as a potential therapeutic target in LUAD.

The Hippo pathway, first discovered in Drosophila (1), plays an important role in regulating the size of tissues and organs, and maintains homeostasis by modulating cell proliferation and apoptosis. The Hippo pathway itself is regulated by intrinsic cell signals, such as cell polarity, cell-cell contact, and by the actin cytoskeleton (2).

The Hippo pathway, first discovered in Drosophila (1), plays an important role in regulating the size of tissues and organs, and maintains homeostasis by modulating cell proliferation and apoptosis. The Hippo pathway itself is regulated by intrinsic cell signals, such as cell polarity, cell-cell contact, and by the actin cytoskeleton (2).

Non-functioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. The elucidation of the mechanisms of aggressive NFPAs in bone destruction is required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, we investigated the differential proteomics of fibroblasts isolated from clinical specimens of NFPAs with or without bone destruction. Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction NFPAs (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. Furthermore, immunohistochemical staining of the NFPAs clinical samples showed that the expression of caldesmon in stromal cells and the expression of osteopontin in both tumor cells and stroma were significantly increased in BD-NFPAs. Taken together, our results indicate a possible way that osteopontin secreted from both NFPA cells and surrounding fibroblasts modify caldesmon expression and polymerization in fibroblasts, which may contribute to bone destruction in NFPA patients.

MicroRNA expression profiling assays have shown that miR-34b/c and miR-449a are down-regulated in nasopharyngeal carcinoma ( NPC); however, the targets and functions of miR-34b/c and miR-449a in the pathologenesis of NPC remain elusive. In this study, we verified miR-34b/c and miR-449a were significantly reduced with the advance of NPC. Overexpression of miR-34b-3 and miR-449a suppressed the growth of NPC cells in culture and mouse tumor xenografts. Using tandem mass tags for quantitative labeling and LC-MS/MS analysis to investigate protein changes after restoring expression of miR-34b-3, 251 proteins were found to be down-regulated after miR-34b-3 transfection. Through 3 replicate experiments, we found that miR-34b-3 regulated the expression of 15 potential targeted genes mainly clustered in the key enzymes of glycolysis metabolism, including lactate dehydrogenase A ( LDHA). Further investigation revealed that miR-34b-3 and miR-449a negatively regulated LDHA by binding to the 3' untranslated regions of LDHA. Furthermore, LDHA overexpression rescued the miR-34b-3 and miR-449a induced tumor inhibition effect in CNE2 cells. In addition, miR-34b-3 and miR-449a suppressed LDH activity and reduced LD content, which were directly induced by downregulation of the LDHA. Our findings suggest that miR-34b-3 and miR-449a suppress the development of NPC through regulation of glycolysis via targeting LDHA and may be potential therapeutic targets for the treatment of NPC.