ABSTRACT
Lung adenocarcinoma (LUAD) accounts for almost 40% of lung cancers, leading to significant associated morbidity and mortality rates. However, the mechanism of LUAD tumorigenesis remains far from clear. Here, we scanned down-regulated genes involved in LUAD sourced from The Cancer Genome Atlas and Gene Expression Omnibus data and focused on G protein-coupled receptor 133 (GPR133). We offer compelling evidence that GPR133 was expressed at low levels in the setting of LUAD, and higher expression was positively related to a better prognosis among patients with LUAD. Functionally, GPR133 inhibited cell proliferation and tumor growth in vitro and in vivo. Regarding the mechanism, flow cytometry assays and western blot assays showed that GPR133 enhanced p21 and decreased cyclin B1 expression, thus triggering LUAD cells at G2/M-phase arrest. Consistent with this, we evaluated the expression levels of cell-cycle biomarkers and found that bioinformatics analysis combined with N6 -methyladenosine (methylation at the N6 position in adenosine) RNA immunoprecipitation-qPCR assay indicated that GPR133 expression was down-regulated by this modification. Moreover, we observed that methyltransferase-like 3 was impaired in LUAD, and that it is able to significantly increase levels of GPR133 by enhancing its RNA stability. In conclusion, we found that GPR133 expression was down-regulated in LUAD via N6 -methyladenosine modification. Increasing GPR133 levels could suppress LUAD cell proliferation and tumor growth.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Adenocarcinoma of Lung/metabolism , Cell Proliferation/genetics , Humans , Lung Neoplasms/metabolism , RNA , Receptors, G-Protein-Coupled/geneticsABSTRACT
PURPOSE: To investigate the role and mechanism of long non-coding (lnc) RNA LINC00339 in pancreatic cancer (PANC), and provided a potential target for its biological diagnosis and treatment. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00339 in PANC tissue specimens and cell lines. The experimental cell lines differentially expressing LINC00339 were constructed by using small interfering RNA and lentivirus transfection. Cell proliferation was examined by cell counting kit-8 (CCK-8) and colony formation experiments and transwell experiments were used to assess cell invasion and migration abilities. The luciferase assay and RNA immunoprecipitation (RIP) were employed to study the target gene for LINC00339, and western blot analysis was utilized to measure protein expression of the downstream gene. RESULTS: The level of LINC00339 expression in PANC tissues or cells was significantly higher than that in their respective control groups. Interfering expression of LINC00339 could notably inhibit the proliferation, invasion and migration of SW1990 cells, while the over-expressing expression of LINC00339 obviously increased the growth and metastasis abilities of PANC-1 cells. LINC00339 could act as a miR-497-5p sponge, adsorbing miR-497-5p, thereby inhibiting its action by increasing the expression of its target gene IGF1R. The expression of miR-497-5p and its target gene IGF1R could be significantly altered by altering the expression of LINC00339. CONCLUSIONS: LINC00339 was markedly over-expressed in PANC tissues and cells and promoted cell proliferation, invasion, and migration via sponging miR-497-5p, thereby increasing IGF1R expression. Our study could provide a novel target for PANC diagnosis and biotherapy.
Subject(s)
MicroRNAs/genetics , Pancreatic Neoplasms/genetics , RNA, Long Noncoding/genetics , Receptors, Somatomedin/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Neoplasm Metastasis , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Receptor, IGF Type 1 , Signal TransductionABSTRACT
OBJECTIVE: Inflammatory markers may be associated with mortality in the elderly population. We conducted this meta-analysis to evaluate the association of elevated circulating interleukin-6 levels with cardiovascular or all-cause mortality in the general elderly population. METHODS: A comprehensive literature search was conducted through the Pubmed and Embase databases until April 2016. Prospective observational studies that investigated the association of circulating interleukin-6 levels with cardiovascular or all-cause mortality in the elderly general population (aged 60 years or more) were included. Pooled risk ratio (RR) and 95% confidence intervals (CI) were calculated by the highest vs. the lowest interleukin-6 levels. RESULTS: Nine prospective studies involving 9087 participants were identified. When comparing the highest with the lowest interleukin-6 levels, the pooled RR of all-cause mortality and cardiovascular mortality were 1.49 (95% CI 1.33-1.67) and 1.69 (95% CI 1.27-2.25), respectively. Subgroup analysis indicated the effects of interleukin-6 on all-cause mortality were consistently observed in sample sizes, region, durations of follow-up, interleukin-6 cutoff value and number of adjusted for covariates subgroups. CONCLUSIONS: This meta-analysis indicates that elevated circulating interleukin-6 levels are independently associated with greater risk of cardiovascular and all-cause mortality in the general elderly population.
