LncRNA LINC01116 sponges miR-93-5p to promote cell invasion and migration in small cell lung cancer.

BACKGROUND: LINC01116 is a recently identified oncogenic lncRNA in glioma. Differential expression analysis using the public gene expression analysis tool GEPIA revealed the upregulation of LINC01116 in lung cancer. We studied the functions of LINC01116 in small cell lung cancer (SCLC). METHODS: The expression of LINC01116 in several types of cancer tissue and the paired non-tumor tissues was evaluated by GEPIA. The effects of the overexpression of LINC01116 and miR-93-5p on the expression of STAT3 were evaluated. The effects of the overexpression of LINC01116, miR-93-5p and STAT3 on SHP-77 cell behaviors were evaluated by Transwell assays. RESULTS: LINC01116 was highly expressed in SCLC and predicted poor survival. In SCLC tissues, the expression of LINC01116 was positively correlated with STAT3. Bioinformatics analysis revealed that miR-93-5p may target LINC01116. Overexpression of LINC01116 increased STAT3 but did not affect the expression of miR-93-5p. Transwell assay showed that LINC01116 and STAT3 increased cell invasion and migration rates. MiR-93-5p played an suppressed cell behaviors and suppressed the role of LINC01116. CONCLUSION: Therefore, LINC01116 might upregulate STA3 by sponging miR-93-5p, thereby promoting cell invasion and migration in SCLC.

CtBP1 promotes tumour-associated macrophage infiltration and progression in non-small-cell lung cancer.

The progression of lung cancer is majorly facilitated by TAMs (tumour-associated macrophages). However, how the TAMs infiltrate the NSCLC microenvironment and the associated biochemical are not fully elaborated. Research has revealed that changes in CtBP1 modulates innate immunity. Here, we investigated if CtBP1 facilitates infiltration of TAM and the subsequent progression of NSCLC. Immunohistochemical analysis was carried out in 96 NSCLC patients to estimate the clinicopathological importance of CtBP1 in the disease. CtBP1 overexpression and knockdown were carried out to assess the activity of CtBP1 in NSCLC cells. Elevated expression of CtBP1 correlated positively with TAMs infiltration into NSCLC tissues, induced EMT (epithelial-mesenchymal transition) in NSCLC cells and modulated the activated NF-κB signalling pathway leading to increase in CCL2 secretion from NSCLC cells, thus promoting TAM recruitment and polarization. TAM induction and polarization reduced significantly on exhausting p65 in NSCLC cells with CtBP1. Moreover, infiltration of TMAs was reduced remarkably on antagonist-mediated blocking of CCR2 and impeded the progression of NSCLC in a mouse model. These findings thus show a novel insight into the process of CtBP1-regulated TAM infiltration in NSCLC.

The clinical and prognostic impact of aldehyde dehydrogenase 1 in non-small cell lung cancer: a meta-analysis.

BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a cancer stem cell marker. However, the clinical role of ALDH1 in non-small cell lung cancer (NSCLC) remains conflicting. This study was conducted to investigate the correlation of ALDH1 with NSCLC patients' clinicopathological characteristics and prognosis. METHODS: The electronic databases were searched for the available literature. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) or hazard ratios (HRs: multivariate Cox analysis) with 95% CIs were used to evaluate the impact of ALDH1 on NSCLC. RESULTS: Final 13 eligible studies with 2,407 patients published between 2009 and 2019 were identified. ALDH1 expression was not correlated with age, gender, smoking behavior, clinical stage, histological grade, lymph node metastasis, and distal metastasis, but the results demonstrated a positive association of ALDH1 expression with recurrence (yes vs. no: OR =2.82, 95% CI, 1.17-6.80, P=0.021) and a negative association of ALDH1 expression with vascular invasion (positive vs. negative: OR =0.63, 95% CI, 0.41-0.98, P=0.04). ALDH1 expression was significantly lower in adenocarcinoma (AD) than in squamous cell carcinoma (SCC) (OR =0.39, 95% CI, 0.30-0.51, P<0.001). Multivariate Cox analysis showed that ALDH1 expression was not associated with overall survival (OS) and disease-free survival (DFS), but was correlated with improved disease-specific survival (DSS) (HR =0.47, 95% CI, 0.22-0.98, P=0.043). CONCLUSIONS: ALDH1 expression may be an independent favorable prognostic marker for DSS in NSCLC.

Silencing NID2 by DNA Hypermethylation Promotes Lung Cancer.

To characterize the DNA methylation as well as exploring the relationship between NID2 methylation and the lung cancer development. Collecting chip data of 9 lung cancer samples and 11 adjacent normal samples from the Gene Expression Omnibus database. Tissues and cells NID2 gene methylation level was measured by methylation-specific PCR. NID2 mRNA level and protein level were validated by Real-Time PCR and Western blot separately. Functional study of lung cancer cells was performed with Cell Counting Kit-8 assay. Colony formation assay, transwell assay, wound healing assay and low cytometry were performed. Finally, NID2 tumorigenesis in vivo was tested in nude mice xenograft models. Microarray analysis outcome present NID2 hypermethylation status in lung cancer tissues. High methylation and low mRNA expression levels of NID2 were detected. After NID2 demethylation or overexpression in cancer cells, cell viability, proliferation, migration as well as invasion ability decreased. Nevertheless, a significant enhancement in apoptosis rate were observed. Overexpressing NID2 or demethylation in lung cancer cells inhibited the tumorigenesis of lung cancer in nude mice. The mRNA and protein level of NID2 in tumors obtained from nude mice xenograft were unanimous with the in vitro assays' outcome, which significantly decreased after overexpressing NID2 or demethylation. NID2 methylation reduces its expression level and promotes the development of lung cancer.