BIRC3-HSP90B1 Interaction Inhibits Non-Small Cell Lung Cancer Progression through the Extracellular Signal-Regulated Kinase Pathway.

The long-term prognosis of nonsmall cell lung cancer (NSCLC) remains unsatisfactory, which is a major challenge in lung cancer treatment. BIRC3 is an inhibitor of apoptosis (IAP) protein that contributes to tumor regulation. However, the underlying regulatory mechanisms of BIRC3 in NSCLC remains unknown. We initiated an analysis of BIRC3 expression data in NSCLC tumors and adjacent tissues using the TCGA and GEO databases and examined the variations in prognosis. Further, we conducted overexpression (OE) and knockdown (KD) studies on BIRC3 to evaluate its effects on NSCLC cell proliferation, migration, and invasion. Additionally, through utilization of a nude mouse model, the regulatory effects of BIRC3 on NSCLC were verified in vivo. Co-immunoprecipitation (Co-IP) assay served to pinpoint the proteins with which BIRC3 interacts. The results indicated that BIRC3 is down-regulated in NSCLC tissues and that patients with high BIRC3 expression demonstrate a better prognosis. BIRC3 is a tumor suppressor, inhibiting the proliferation and metastasis of NSCLC. Co-IP results revealed that BIRC3 interacts with HSP90B1, leading to a decrease in HSP90B1 expression and subsequent negative regulation of the ERK signaling pathway. BIRC3 may serve as a prognostic biomarker for NSCLC. It directly interacts with HSP90B1 to negatively regulate the ERK signaling pathway, thereby hindering the progression of NSCLC.

Novel long non-coding RNA CYB561-5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non-small cell lung cancer.

Abnormally expressed long non-coding RNAs (lncRNAs) have been recognized as potential diagnostic biomarkers or therapeutic targets in non-small cell lung cancer (NSCLC). The role of the novel lnc-CYB561-5 in NSCLC and its specific biological activity remain unknown. In this study, lncRNAs highly expressed in NSCLC tissue samples compared with paired adjacent normal tissue samples and atypical adenomatous hyperplasia were identified by RNA-seq analysis. Lnc-CYB561-5 is highly expressed in human NSCLC and is associated with a poor prognosis in lung adenocarcinoma. In vivo, downregulation of lnc-CYB561-5 significantly decreases tumour growth and metastasis. In vitro, lnc-CYB561-5 knockdown treatment inhibits cell migration, invasion and proliferation ability, as well as glycolysis rates. In addition, RNA pulldown and RNA immunoprecipitation (RIP) assays show that basigin (Bsg) protein interacts with lnc-CYB561-5. Overall, this study demonstrates that lnc-CYB561-5 is an oncogene in NSCLC, which is involved in the regulation of cell proliferation and metastasis. Lnc-CYB561-5 interacts with Bsg to promote the expression of Hk2 and Pfk1 and further lead to metabolic reprogramming of NSCLC cells.

Efficient poly(3-hydroxybutyrate-co-lactate) production from corn stover hydrolysate by metabolically engineered Escherichia coli.

Poly(3-hydroxybutyrate-co-lactate)[P(3HB-co-LA)], is a biodegradable and biocompatible bioplastic, and the monomeric composition of the copolymer plays an important role in affecting its mechanical properties. Corn stover hydrolysate (CSH), the waste by-product in agriculture, has been considered as an important carbon source for value-added biochemical production. Therefore, the effect of CSH on P(3HB-co-LA) biosynthesis was investigated in this study. Taking CSH as the carbon source, the lactate (LA) fraction in the copolymer reached 7.1 mol% by the engineered stain. The results of shake flask fermentation demonstrated that reducing the activity of electron transport system resulted in a higher LA fraction. Furthermore, we replaced the promoter of the key gene pctth with ldhA gene promoter, so that the expression of pctth gene could be dynamically modulated as well as the lactic acid content changed. This study suggests that CSH is a promising carbon source for the production of biodegradable P(3HB-co-LA).

[Effect of short-chain thioesterase deficiency on P(3HB-co-LA) biosynthesis in Escherichia coli].

Polyhydroxyalkanoates (PHAs) have obtained much attention in biomaterial fields due to their similar physicochemical properties to those of the petroleum-derived plastics. Poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] is one member of the PHAs family, and has better toughness and transparency compared to existing polylactic acid (PLA) and poly[(R)-3-hydroxybutyrate] [P(3HB)]. First, we confirmed the one-step biosynthesis of P(LA-co-3HB) with the lactate fraction of 23.8 mol% by introducing P(3HB-co-LA) production module into Escherichia coli MG1655. Then, the lactate fraction was increased to 37.2 mol% in the dld deficient strain WXJ01-03. The genes encoding the thioesterases, ydiI and yciA, were further knocked out, and the lactate fraction in the P(3HB-co-LA) was improved to 42.3 mol% and 41.1 mol% respectively. Strain WXJ03-03 with dld, ydiI and yciA deficient was used for the production of the LA-enriched polymer, and the lactate fraction was improved to 46.1 mol%. Notably, the lactate fraction in P(3HB-co-LA) from xylose was remarkably higher than from glucose, indicating xylose as a potent carbon source for P(3HB-co-LA) production. Therefore, the deficiency of thioesterase may be considered as an effective strategy to improve the lactate fraction in P(3HB-co-LA) in xylose fermentation.

High developmental pluripotency­associated 4 expression promotes cell proliferation and glycolysis, and predicts poor prognosis in non­small­cell lung cancer.

The developmental pluripotency­associated 4 (Dppa4) gene serves critical roles in cell self­renewal, as well as in cancer development and progression. However, the regulatory role of Dppa4 in non­small­cell lung cancer (NSCLC) and its underlying mechanisms remain elusive. The aim of the present study was to investigate the biological function of Dppa4 in NSCLC and its underlying mechanism of action. Dppa4 expression was measured in NSCLC tissue samples and cell lines, and its effect on cell proliferation and the expression of glycolytic enzymes was determined. In addition, the underlying mechanisms of Dppa4­induced alterations in glycolysis were analyzed. Univariate and multivariate analyses were also performed to analyze the prognostic significance of clinicopathological characteristics. Dppa4 was found to be highly expressed in NSCLC tissues and cell lines. Furthermore, it was observed that Dppa4 was correlated with the degree of tumor differentiation and TNM stage. Univariate and multivariate analyses identified Dppa4 expression and clinical stage as prognostic factors for NSCLC patients. Kaplan­Meier analysis further revealed that patients with lower Dppa4 expression exhibited a better prognosis. In NSCLC cells, Dppa4 knockdown inhibited cell proliferation, while Dppa4 overexpression enhanced cell proliferation, which was likely mediated by glycolysis promotion. Dppa4 knockdown had no evident effect on the majority of enzymes examined; however, glucose transporter type 4 (GLUT­4) and pyruvate kinase isozyme M2 were significantly upregulated, and hexokinase II (HK­II) and lactate dehydrogenase B (LDHB) were downregulated following Dppa4 knockdown. By contrast, Dppa4 overexpression resulted in downregulation of GLUT­4, and upregulation of HK­II, enolase and LDHB, whereas it had no effect on other enzymes. Since the most evident effect was observed on LDHB, further functional experiments demonstrated that this enzyme reversed the promoting effects of Dppa4 in NSCLC. In conclusion, Dppa4 promotes NSCLC progression, partly through glycolysis by LDHB. Thus, the Dppa4­LDHB axis critically contributes to glycolysis in NSCLC cells, thereby promoting NSCLC development and progression.