BackgroundLong noncoding RNAs (lncRNAs) are an important class of functional regulators involved in human cancers development, including gastric cancer (GC). Studying aberrantly expressed lncRNAs may provide us with new insights into the occurrence and development of gastric cancer by acting as oncogenes or tumor suppressors. In this study, we aim to examine the expression pattern of lncRNA HAGLROS in GC and its clinical significance as well as its biological role in tumor progression.MethodsBioinformatics analysis and qRT-PCR were performed to detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or loss of function approaches were used to investigate the biological functions of HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony formation assay and nude mouse xenograft model. Wound healing and Transwell assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA-seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to measure molecular mechanisms. Results are shown as means ± S.D. and differences were tested for significance using Student’s t-test (two-tailed).ResultsWe screened out HAGLROS, whose expression was significantly increased and correlated with outcomes of GC patients by publicly available lncRNAs expression profiling and integrating analyses. Exogenous down-regulation of HAGLROS expression significantly suppressed the cell proliferation, invasion and migration. Mechanistic investigations showed that HAGLROS was a direct target of transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR expression and increased autophagy-related genes ATG9A and ATG9B expression. Further investigation showed that HAGLROS regulated mTOR signals in two manners. In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling pathway which was known to be an important negative signal of autophagy. Here activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells.ConclusionThe present study demonstrates that HAGLROS overexpression contributes to GC development and poor prognosis and will be a target for GC therapy and further develop as a potential prognostic biomarker.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0756-y) contains supplementary material, which is available to authorized users.

Long non-coding RNA HOX transcript antisenseRNA (HOTAIR) has been widely identified to participate in tumour pathogenesis, acting as a promoter in colorectal cancer carcinogenesis. However, the association between genetic variants in HOTAIR and cancer risk has not yet been reported. In the present study, we performed a two-stage case-control study to investigate the association between HOTAIR tagSNPs and the risk of colorectal cancer. We found that individuals with rs7958904 CC genotype had a significantly decreased risk of colorectal cancer in both Stage 1 and 2, compared with those carrying GG genotype [odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.51-0.97 in Stage 1; OR = 0.58, 95% CI = 0.37-0.91 in Stage 2; OR = 0.67, 95% CI = 0.51-0.87 in combined stage]. The subsequently stratified analyses showed that the protective effect of rs7958904 was more pronounced in several subgroups. In summary, our study showed that genetic variants in HOTAIR were associated with risk of colorectal cancer and rs7958904 may act as a potential biomarker for predicting the risk of colorectal cancer.

Genome-wide association studies (GWASs) have identified multiple susceptibility loci for colorectal cancer, but much of heritability remains unexplained. To identify additional susceptibility loci for colorectal cancer, here we perform a GWAS in 1,023 cases and 1,306 controls and replicate the findings in seven independent samples from China, comprising 5,317 cases and 6,887 controls. We find a variant at 12p13.2 associated with colorectal cancer risk (rs2238126 in ETV6, P=2.67 × 10−10). We replicate this association in an additional 1,046 cases and 1,076 controls of European ancestry (P=0.034). The G allele of rs2238126 confers earlier age at onset of colorectal cancer (P=1.98 × 10−6) and reduces the binding affinity of transcriptional enhancer MAX. The mRNA level of ETV6 is significantly lower in colorectal tumours than in paired normal tissues. Our findings highlight the potential importance of genetic variation in ETV6 conferring susceptibility to colorectal cancer.

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Published data regarding the association between the apurinic/apyrimidinic endonuclease 1 (APE1) T1349G (Asp148Glu) polymorphism and cancer risk show inconclusive results. To derive a more precise estimation of the relationship, we performed a meta-analysis of 27 published studies that included 12 432 cancer cases and 17 349 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the strength of the associations. The overall results suggested that the variant genotypes were associated with a moderately increased risk of all cancer types (OR = 1.09, 95% CI = 1.01-1.18 for TG versus TT; OR = 1.08, 95% CI = 1.00-1.18 for GG/TG versus TT). In the stratified analyses, the risk remained for studies of colorectal cancer, European populations and population-based studies. Although some modest bias could not be eliminated, this meta-analysis supported that the APE1 T1349G polymorphism is a low-penetrance risk factor for cancer development.