Construction of a Lung Adenocarcinoma Prognostic Model Utilizing Serine and Glycine Metabolism-Related Genes.

The objective of this study was to construct a prognostic model by utilizing serine/glycine metabolism-related genes (SGMGs), thus establishing a risk score for lung adenocarcinoma (LUAD). Based on the TCGA-LUAD and SGMG data set, two subtypes with different SGMG expression levels were identified by clustering analysis. Thirteen differential expression genes were used to construct RiskScore by Cox regression. GSE72094 data set was used for validation. The survival characteristics, immune features, and potential benefits of chemotherapy drugs were analyzed for two risk groups. RiskScore was constructed based on the genes ABCC12, RIC3, CYP4B1, SFTPB, CACNA2D2, IGF2BP1, NTSR1, DKK1, CREG2, PITX3, RGS20, FETUB, and IGFBP1. Patients in the low-risk (LR) group exhibited a superior overall survival. In addition, aDCs, iDSs, mast cells, neutrophils, HLA, and type II IFN were more abundant in the LR group with higher IPS scores and lower TIDE scores. In contrast, NK cells, APC coinhibition, and MHC-I were more common in the high-risk (HR) group, which may be more sensitive to chemotherapy drugs such as cisplatin, oxaliplatin, and nilotinib. RiskScore was a promising biomarker that can be used to distinguish LUAD prognosis, immune features, and sensitivity to chemotherapy drugs.

NCAPG stimulates lung adenocarcinoma cell stemness through aerobic glycolysis.

BACKGROUND: Cancer stem cells are pivotal in cancer progression and therapy, including lung adenocarcinoma (LUAD). High NCAPG level is implicated in malignant tumorigenesis, but investigations on NCAPG and LUAD stem cells are warranted. Hence, projecting the impact of NCAPG on cell stemness and the targeted therapy for LUAD is of the essence. METHODS: Bioinformatics analyzed NCAPG expression in LUAD tissues. qRT-PCR assayed NCAPG expression in LUAD cells. CCK-8 assessed cell viability and cell sphere-forming assay measured sphere-forming ability. Western blot assessed expression of stem cell-related markers (CD133, CD44, Oct-4) and specific genes (HK2, PKM2, LDHA) related to glycolysis metabolism pathway. Cellular glycolytic capacity was assayed by glycolytic metabolites pyruvic acid, lactate, citrate, and malate assay kits, and extracellular acidification rate and oxygen consumption rate analyzers. RESULTS: NCAPG was upregulated in LUAD and enriched in the aerobic glycolysis pathway, and its expression was positively correlated with that of glycolytic marker genes. Cell function assays revealed that NCAPG stimulated proliferation, stemness, and glycolytic activity of LUAD cells. Rescue experiments unveiled that 2-DG (glycolysis inhibitor) was able to reverse the stimulative impact of NCAPG overexpression on proliferation, stemness, and glycolytic activity of LUAD cells. CONCLUSION: NCAPG stimulated LUAD cell stemness through activation of glycolysis pathway. NCAPG may be possible biomarker for diagnosis and target for treatment of LUAD.

Role of STAT3 Expression in Thyroid Cancer: A Meta-Analysis and Systematic Review Based on the Chinese Population.

Background: Signal transduction and activator of transcription 3 (STAT3) is an oncogene with transcriptional activity. In recent years, there have been several studies concerning the clinicopathological significance of the expression of the STAT3 protein in thyroid cancer. However, the results are still inconsistent. In this study, we conducted a meta-analysis to evaluate the relationship between the expression of STAT3 protein and thyroid cancer susceptibility and its clinicopathological characteristics. Methods: We searched the China National Knowledge Infrastructure (CNKI) database, Chinese Biomedical Literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wanfang, PubMed, and EMBASE. The time frame of the publication search was from the establishment of each of the databases until December 2021. We performed a meta-analysis to quantitatively evaluate the relationship between the expression of the STAT3 protein in thyroid cancer and its clinicopathological characteristics. Results: A total of eight articles were included in the meta-analysis, covering 448 thyroid cancer patients and 227 controls. Results indicated that the expression of STAT3 protein in thyroid cancer tissue is highly expressed (OR = 14.41, 95% CI (6.94, 29.91), p < 0.001). Besides, we also discovered that STAT3 protein is negatively correlated with thyroid cancer tumor diameter and TNM stage (OR = 0.13, 95% CI (0.05, 0.33), p < 0.001; OR = 0.40, 95% CI (0.24, 0.67), p < 0.001) and positively correlated with lymph node metastasis (OR = 2.83, 95% CI (1.08, 7.46), p = 0.035). However, STAT3 expression is not related to gender (OR = 0.88, 95% CI (0.54, 1.44), p = 0.609), age (OR = 0.54, 95% CI (0.21, 1.36), p = 0.191), capsular invasion (OR = 2.98, 95% CI (0.23, 38.29), p = 0.403), or tumor multiplicity (OR = 0.25, 95% CI (0.003, 19.28), p = 0.533). Conclusions: This study reveals that STAT3 protein expression is significantly related to the susceptibility and clinicopathological characteristics of thyroid cancer. It also suggests that STAT3 may be a potential predictor of the clinical progression of thyroid cancer.

Circular RNA hsa_circ_0023404 promotes proliferation, migration and invasion in non-small cell lung cancer by regulating miR-217/ZEB1 axis.

BACKGROUND: Circular RNAs (circRNAs) have been considered as key regulators of cancer biology. However, the functional role of hsa_circ_0023404 in non-small cell lung cancer (NSCLC) and its regulatory mechanism are still almost unknown. METHODS: The expression of hsa_circ_0023404, miR-217 and zinc finger E-box-binding homeobox 1 (ZEB1) was evaluated by quantitative real-time polymerase chain reaction. The role of hsa_circ_0023404 in NSCLC progression was determined using cell count kit-8 assay, transwell migration and invasion assay. Luciferase reporter assay was performed to assess the interaction of hsa_circ_0023404, miR-217 and ZEB1 in NSCLC cells. RESULTS: The expression of hsa_circ_0023404 was upregulated in NSCLC tissues, as well as in NSCLC cell lines. High hsa_circ_0023404 expression predicted short overall survival in NSCLC. Functionally, knockdown of hsa_circ_0023404 inhibited the proliferation, migration and invasion of NSCLC cells. In the further molecular mechanism study, hsa_circ_0023404 was shown to interact with miR-217/ZEB1 axis to contribute to the growth of NSCLC cells. CONCLUSION: hsa_circ_0023404 promotes the proliferation, migration and invasion of NSCLC cells by regulating miR-217/ZEB1 axis, providing a fresh perspective on circRNAs in NSCLC development.