Background. Long noncoding RNA-based prognostic biomarkers have demonstrated great potential in the diagnosis and prognosis of cancer patients. However, systematic assessment of a multiple lncRNA-composed prognostic risk model is lacking in stomach adenocarcinoma (STAD). This study is aimed at constructing a lncRNA-based prognostic risk model for STAD patients. Methods. RNA sequencing data and clinical information of STAD patients were retrieved from The Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNAs (DElncRNAs) were identified using the R software. Univariate and multivariate Cox regression analyses were performed to construct a prognostic risk model. The survival analysis, C-index, and receiver operating characteristic (ROC) curve were employed to assess the sensitivity and specificity of the model. The results were verified using the GEPIA online tool and our clinical samples. Pearson correlation coefficient analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to indicate the potential biological functions of the selected lncRNA. Results. A total of 1917 DElncRNAs were identified from 343 cases of STAD tissues and 30 cases of noncancerous tissues. According to univariate and multivariable Cox regression analyses, four DElncRNAs (AC129507.1, LINC02407, AL022316.1, and AP000695.2) were selected to establish a prognostic risk model. There was a significant difference in the overall survival between high-risk patients and low-risk patients based on this risk model. The C-index of the model was 0.652. The area under the curve (AUC) for the ROC curve was 0.769. GEPIA results confirmed the expression and prognostic significance of AP000695.2 in STAD. Our clinical data confirmed that upregulated expression of AP000695.2 was correlated with the T stage, distant metastasis, and TNM stage in STAD. GO and KEGG analyses demonstrated that AP000695.2 was closely related to the tumorigenesis process. Conclusions. In this study, we constructed a lncRNA-based prognostic risk model for STAD patients. Our study will provide novel insight into the diagnosis and prognosis of STAD patients.

Aim: CC chemokine receptor 9 (CCR9) interacts with its exclusive ligand CCL25, resulting in promoting tumor progression and metastasis. However, the effect and mechanisms of CCR9 on lung adenocarcinoma distant metastasis remain largely unknown. To preliminary clarify the underlying mechanisms, we investigate the correlation between CCR9 and ALDH1A1 + cancer stem cells (CSCs), as well as the effect of CCR9 on the migration and invasion of CSCs. Methods: Immunohistochemistry was performed to detect the expression of CCR9 in lung adenocarcinoma tissues. The correlations of CCR9 with distant metastasis and overall survival were investigated. Serial paraffin-embedded tissue blocks were used to detect ALDH1A1 + CSCs expression. The correlations between CCR9 expression and ALDH1A1 + CSCs were evaluated. We further studied the effect of CCR9/CCL25 on the migration and invasion of CSCs using transwell assays. Results: There were positive correlations between CCR9 expression and distant metastasis, as well as poor overall survival. Patients with high CCR9 expression were more likely to develop distant metastasis and demonstrated poorer overall survival than patients with low CCR9 expression. In addition, there was positive correlation between the expression of CCR9 and ALDH1A1 in the same tumor microenvironment. ALDH high CSCs demonstrated enhanced expression of CCR9 than ALDH low cells. Further transwell assays demonstrated that the numbers of CSCs migrated or invaded in response to CCL25 were more than that without CCL25 stimulation. Additional application of anti-CCR9 antibody reversed the CCL25-induced migration and invasion of CSCs. Conclusions:In summary, our study demonstrated that CCR9/CCL25 promoted the migration and invasion of CSCs, which might contribute to distant metastasis and poor overall survival. Our findings provided evidence that CCR9/CCL25 could be used as novel therapeutic targets for lung adenocarcinoma.

Background: IL-1β is reported to be involved in cancer development and distant metastasis. However, the underlying mechanism of IL-1β upon malignant behaviors remains largely unknown. In this study, we aimed to study whether IL-1β could enhance the stemness traits of tumor cells. Methods: The concentrations of serum IL-1β in head and neck squamous cell carcinoma (HNSCC) and melanoma patients were detected using ELISA assay. The effect and mechanisms of IL-1β on tumor cell growth, migration, invasion and stemness characters were studied using HNSCC cell SCC7 and melanoma cell B16-F10. The underlying mechanisms were further explored. Results: Enhanced concentrations of IL-1β were positively correlated with advanced tumor stage in both HNSCC and melanoma patients. IL-1β treatment led to a significant increase in tumor growth both in vitro and in vivo. IL-1β stimulation promoted cell proliferation, colony formation and tumorigenicity. In addition, IL-1β-stimulated tumor cells gained enhanced capabilities on wounding healing and invasion capabilities. Moreover, IL-1β stimulation promoted the stem-like capabilities of both HNSCC cells and melanoma cells, including the enrichment of aldehyde dehydrogenase + (ALDH +) cells, up-regulation of stem cell related markers Nanog, OCT4, and SOX2, sphere formation and chemoresistance. Mechanistically, IL-1β treatment promoted the phosphorylation of Smad1/5/8 and activated its downstream target inhibitor of differentiation 1 (ID1). Silencing ID1 abrogated sphere formation and upregulated expression of stemness genes which were induced by IL-1β stimulation. Conclusion: Our data demonstrates that IL-1β promotes the stemness of HNSCC and melanoma cells through activating Smad/ID1 signal pathway.

Little is known about the biological functions of neuron-specific enolase (NSE) as a specific biomarker for small-cell lung cancer (SCLC). Herein, we elucidate the effect and mechanism of NSE on SCLC stem cell-like characteristics. Upregulated NSE expression was observed in spheroid cells. The gain-of-function and loss-of-function approaches demonstrated that modulation of NSE positively regulated cell proliferation, drug resistance, spherical clone formation, tumor growth, and stem cell-like characteristics of SCLC cells. Mechanistic studies revealed that NSE might downregulate the expression of neuroblastoma suppressor of tumorigenicity 1 (NBL1) by interacting with NBL1, thereby attenuating the competitive inhibitory effect of NBL1 on BMP2 and enhancing the interaction between BMP2 and BMPR1A; this, in turn, may activate the BMP2/Smad/ID1 pathway and promote SCLC stem cell-like characteristics. Moreover, overexpression of NBL1or knockdown of BMP2 rescued the NSE-induced stem cell-like characteristics. In clinical specimens, NSE expression was positively associated with ALDH1A1 expression and negatively correlated with NBL1 expression. High NSE and ALDH1A1 expressions and low NBL1 expression were correlated with poor prognosis in patients with SCLC. In summary, our study demonstrated that NSE promoted stem cell-like characteristics of SCLC via NBL1 and the activation of the BMP2/Smad/ID1 pathway.