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Purpose: Long noncoding RNAs (lncRNAs) are emerging as gene regulators to drive many important cancer phenotypes through interaction with microRNAs. There have been numerous data about upregulation of H19 and its strong oncogenic function in progression of cancers. However, the function and detailed mechanisms of H19 on small cell lung cancer (SCLC) are still unclear. Methods: In this study, we investigated H19 expression in SCLC and para-carcinoma tissues. We also explored the function and detailed mechanisms of H19 on SCLC cells via RT-PCR, transwell assay, Western blot, dual-luciferase report assay and RNA pull-down experiments.Results: In this study, we observed that H19 was upregulated in SCLC compared with paracarcinoma tissues or NSCLC tissues. We also uncovered that H19 could promote proliferation and migration of SCLC cells. Functional investigation illustrated that H19 acted as a sponge for miR-140-5p to regulate its expression in SCLC. Interestingly, we further found that H19 upregulated FGF9 expression to promote SCLC progression via sponging miR-140-5p. H19 and FGF9 were also revealed to have similar expression patterns in clinical SCLC samples. Conclusion: These data demonstrated that H19 might be a promising prognostic and therapeutic target for SCLC.

Long noncoding RNAs (lncRNAs) have emerged as regulators of gene expression and play critical regulatory roles in diverse biological functions and diseases, including cancer. In this study, we report the downregulation of LINC01089 in non-small cell lung cancer (NSCLC) samples, relative to adjacent non-tumor tissues, and demonstrate its role in the inhibition of proliferation, migration, and epithelial–mesenchymal transition (EMT) of NSCLC cells. Mechanistic analysis indicates that LINC01089 acts as a sponge for miR-27a, regulating its expression in NSCLC. Interestingly, LINC01089 mediated the upregulation of SFRP1 expression by inhibiting the Wnt/β-catenin–EMT pathway and inhibiting the epithelial–mesenchymal transition of NSCLC via sponging miR-27a. Overall, our findings highlight LINC01089’s tumorigenic role and regulatory mechanism in NSCLC, thereby suggesting its potential as a therapeutic target for managing NSCLC.

BackgroundCD8+ T cells are one of the central effector cells in the immune microenvironment. CD8+ T cells play a vital role in the development and progression of lung adenocarcinoma (LUAD). This study aimed to explore the key genes related to CD8+ T-cell infiltration in LUAD and to develop a novel prognosis model based on these genes.MethodsWith the use of the LUAD dataset from The Cancer Genome Atlas (TCGA), the differentially expressed genes (DEGs) were analyzed, and a co-expression network was constructed by weighted gene co-expression network analysis (WGCNA). Combined with the CIBERSORT algorithm, the gene module in WGCNA, which was the most significantly correlated with CD8+ T cells, was selected for the subsequent analyses. Key genes were then identified by co-expression network analysis, protein–protein interactions network analysis, and least absolute shrinkage and selection operator (Lasso)-penalized Cox regression analysis. A risk assessment model was built based on these key genes and then validated by the dataset from the Gene Expression Omnibus (GEO) database and multiple fluorescence in situ hybridization experiments of a tissue microarray.ResultsFive key genes (MZT2A, ALG3, ATIC, GPI, and GAPDH) related to prognosis and CD8+ T-cell infiltration were identified, and a risk assessment model was established based on them. We found that the risk score could well predict the prognosis of LUAD, and the risk score was negatively related to CD8+ T-cell infiltration and correlated with the advanced tumor stage. The results of the GEO database and tissue microarray were consistent with those of TCGA. Furthermore, the risk score was higher significantly in tumor tissues than in adjacent lung tissues and was correlated with the advanced tumor stage.ConclusionsThis study may provide a novel risk assessment model for prognosis prediction and a new perspective to explore the mechanism of tumor immune microenvironment related to CD8+ T-cell infiltration in LUAD.

Worldwide, lung cancer is the leading cause of cancer death because it has no obvious symptoms initially and often discovered at an advanced stage. 1 Most lung cancer patients have a poor prognosis with an overall 5-year survival rate of 10% to 15%. 2,3 According to different histologic subtypes, lung cancer is divided into adenocarcinoma, squamous cell carcinoma, large cell carcinoma and small cell lung cancer. 4 Of these different histologic subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) constitute the majority of lung cancer subtypes. These two subtypes of lung cancer are derived from different cells and have some evident differences not only in biological patterns and molecular characteristics, but also in therapeutic strategies. 5,6 Ongoing research relating to the epigenetic understanding of lung cancer has made significant progress. Several comprehensive analyses of high-throughput DNA methylation and gene expression emphasized the potential of epigenomics in clinical lung cancer classification. 7 Aberrant DNA methylation patterns are often observed in

Glycogen branching enzyme (GBE1) is a critical gene that participates in regulating glycogen metabolism. However, the correlations between GBE1 expression and the prognosis and tumor-associated macrophages in lung adenocarcinoma (LUAD) also remain unclear. Herein, we firstly analyzed the expression level of GBE1 in LUAD tissues and adjacent lung tissues via The Cancer Genome Atlas (TCGA) database. The effect of GBE1 on prognosis was estimated by utilizing TCGA database and the PrognoScan database. The relationships between the clinical characteristics and GBE1 expression were evaluated via TCGA database. We then investigated the relationships between GBE1 and infiltration of immune cells in LUAD by utilizing the CIBERSORT algorithm and Tumor Immune Estimation Resource (TIMER) database. In addition, we used a tissue microarray (TMA) containing 92 LUAD tissues and 88 adjacent lung tissues with immunohistochemistry staining to verify the association between GBE1 expression and clinical characteristics, as well as the immune cell infiltrations. We found the expression level of GBE1 was significantly higher in LUAD tissues. High expression of GBE1 was associated with poorer overall survival (OS) in LUAD. In addition, high expression of GBE1 was correlated with advanced T classification, N classification, M classification, TNM stage, and lower grade. Moreover, GBE1 was positively correlated with infiltrating levels of CD163+ tumor-associated macrophages in LUAD. In conclusion, the expression of GBE1 is associated with the prognosis and CD163+ tumor-associated macrophage infiltration in LUAD, suggesting that it has potential to be prognostic and immunological biomarkers in LUAD.

Conclusions: MiR-107 suppresses cell proliferation by targeting TRIAP1 in lung cancer. Our finding allows new insights into the mechanisms of lung cancer that is mediated by miR-107.Keywords: miR-107, TRIAP1, proliferation, lung cancer IntroductionLung cancer is the principle cause of global cancerassociated mortality accounting for about 1.59 million deaths every year worldwide [1, 2]. Most of those cases have non-small-cell lung cancer (NSCLC) [3].MicroRNAs (miRNAs) usually negatively modulate gene expression through mRNA cleavage or translational repression [4]. Normally, conserved miRNAs plays a part in many processes, such as cell proliferation, apoptosis, and metabolism. Numerous miRNAs play important roles in cancers as oncogenes or tumour suppressor genes [5][6][7][8][9][10]. MiR-107 is proven to be involved in many cancers, such as colon, breast, gastric, liver, and bladder [11][12][13][14][15][16][17]. It has been reported that miR-107 results in cell cycle arrest to suppress cell proliferation in lung adenocarcinoma [18]. Lowly-expressed miR-107 correlates with tumor development and patient survival in NSCLC [19]. However, it remains unclear how miR-107 works in lung cancer.In the current study, we explored the effect of miR-107 and its novel target gene on proliferation of lung cancer cells. Our findings indicate that TRIAP1 serves as a novel target gene of miR-107 in lung cancer A549 cells. MiR-107 restrains the proliferation of lung cancer cells through regulating TRIAP1. Our finding takes a further step into the mechanism of miR-107-associated lung cancer. Results: QRT-PCR analysis revealed that miR-107 inhibitor or miR-107 was successfully transfected into A549 cells. Western Blot indicated that miR-107 decreased the expression of TRIAP1 protein in the cells. In contrast, miR-107 inhibitor augmented the levels of TRIAP1 protein. Functionally, miR-107 inhibitor remarkably suppressed A549 cell proliferation, whereas, TRIAP1 siRNAs could abrogate the miR-107 inhibitorinduced proliferation of cells. Then, we validated that TRIAP1 was increased in clinical lung cancer samples. MiR-107 expression was negatively related to TRIAP1 expression in clinical lung cancer samples.

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