Role of the CBX Molecular Family in Lung Adenocarcinoma Tumorigenesis and Immune Infiltration.

Background: The members of the Chromobox (CBX) family are important epigenetic regulatory molecules with critical biological roles in many tumors. However, no study has analyzed or verified their role in lung adenocarcinoma (LUAD). Methods: UALCAN and Oncomine databases were used to analyze CBX expression in LUAD, and the cBioPortal database was used to analyze CBX genetic variations. The Kaplan-Meier plotter and UALCAN databases were used to identify molecules with prognostic value. Gene Ontology pathway, receiver operating characteristic curves, and tumor-infiltrating immune cell analyses were used to clarify the biological function of the CBX hub molecules. Paired tumor samples and lung adenocarcinoma cell lines were collected for molecular functional assays to validate the results of the bioinformatics analysis. Results: CBX3/5 may have a cancer-promoting effect and its expression is associated with a poor patient prognosis, while CBX7 shows an opposite trend. CBX3/5/7 can regulate signaling pathways, regulate tumor immune cell infiltration, and has diagnostic value. Molecular biology experiments show that CBX3/5 is highly expressed in LUAD patients; in vitro it promotes the proliferation and migration of the LUAD cell line and can regulate the expression of the corresponding cytokines. CBX7 has opposite effects. Conclusion: Our bioinformatics analysis and subsequent experimental verification confirmed the CBX family members acted as hub signaling molecules in LUAD. The results provide new potential targets for the diagnosis and treatment of this cancer.

Long Noncoding RNA LINC00551 Suppresses Glycolysis and Tumor Progression by Regulating c-Myc-Mediated PKM2 Expression in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a leading cause of mortality associated with cancer globally. Thus, it is essential to elucidate its tumorigenesis and prognosis. Accumulating evidence shows that long noncoding RNAs (lncRNAs) play important roles in the occurrence and progression of tumors by regulating their glucose metabolism. METHODS: Bioinformatics analysis was performed to explore the expression of LINC00551 in LUAD. The level of LINC00551 in LUAD cells and tissues was detected by RT-qPCR. CCK-8, colony formation, EDU and transwell assays were conducted to evaluate the cell growth and migration of LUAD cells (A549 and PC9). High throughput sequencing was used to discover the downstream genes of LINC00551. The metabolic function of LUAD cells was identified by glucose uptake and lactate production assays. Furthermore, tumor xenografts were established to investigate the effects of LINC00551 on tumor growth in vivo. RESULTS: Herein, we found that LINC00551 was low-expressed in LUAD, and its level correlated with clinical prognosis. Ectopic expression of LINC00551 inhibited the proliferation and migration of LUAD cells (A549 and PC9). High throughput sequencing and gene enrichment analysis revealed that LINC0551 may be involved in metabolic pathway. Glucose uptake and lactate production assays suggested that LINC00551 suppressed glycolysis of LUAD cells. Mechanistically, our work revealed that LINC00551 inhibited glycolysis in LUAD cells by impairing c-Myc-mediated transcription of an important glycolysis-related enzyme PKM2. CONCLUSION: In summary, our study identifies LINC00551 as a tumor suppressor in LUAD and implicates the LINC00551/c-Myc/PKM2 axis in the glycolytic remodeling of LUAD.