ABSTRACT
PURPOSE: Studies have found that long noncoding RNA HEIH (lncRNA-HEIH) is upregulated and facilitates hepatocellular carcinoma tumor growth. However, its clinical significances, roles, and action mechanism in colorectal cancer (CRC) remains unidentified. MATERIALS AND METHODS: lncRNA-HEIH expression in CRC tissues and cell lines was measured by quantitative real-time polymerase chain reaction. Cell CountingKit-8, ethynyl deoxyuridine incorporation assay, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and nude mice xenografts assays were performed to investigate the roles of lncRNA-HEIH. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assays were performed to investigate the action mechanisms of lncRNA-HEIH. RESULTS: In this study, we found that lncRNA-HEIH is significantly increased in CRC tissues and cell lines. lncRNA-HEIH expression is positively associated with tumor size, invasion depth, and poor prognosis of CRC patients. Enhanced expression of lncRNA-HEIH promotes CRC cell proliferation and decreases apoptosis in vitro, and promotes CRC tumor growth in vivo. Whereas knockdown of lncRNA-HEIH inhibits CRC cell proliferation and induces apoptosis in vitro, and suppresses CRC tumor growth in vivo. Mechanistically, lncRNA-HEIH physically binds to miR-939. The interaction between lncRNA-HEIH and miR-939 damages the binding between miR-939 and nuclear factor κB (NF-κB), increases the binding of NF-κB to Bcl-xL promoter, and promotes the transcription and expression of Bcl-xL. Moreover, Bcl-xL expression is positively associatedwith lncRNA-HEIH in CRC tissues. Blocking the interaction between lncRNA-HEIH and miR-939 abolishes the effects of lncRNA-HEIH on CRC tumorigenesis. CONCLUSION: This study demonstrated that lncRNA-HEIH promotes CRC tumorigenesis through counteracting miR-939-mediated transcriptional repression of Bcl-xL, and suggested that lncRNA-HEIH may serve as a prognostic biomarker and therapeutic target for CRC.
Subject(s)
Animals , Humans , Mice , Apoptosis , Carcinogenesis , Carcinoma, Hepatocellular , Cell Line , Cell Proliferation , Chromatin Immunoprecipitation , Colorectal Neoplasms , Deoxyuridine , DNA Nucleotidylexotransferase , Heterografts , Immunoprecipitation , In Vitro Techniques , Luciferases , Mice, Nude , Prognosis , Real-Time Polymerase Chain Reaction , Repression, Psychology , RNA , RNA, Long NoncodingABSTRACT
Objective:To study the correlation between serum homocysteine (Hcy) and the staging of gastric cancer,by comparing the concentrations of patients with gastric cancer at different pathological staging.Methods:90 patients with benign gastric diseases and 138 patients with gastric cancer were selected and admitted by Shandong University Qilu Hospital during the date from Mar 2014 to Jun 2015.The patients with gastric cancer were divided into 4 groups,according to the 7th AJCC Cancer Staging.To compare the difference of the concentration levels of Hcy and Tumor marks in different groups and analyze the relationship between benign disease and gastric cancer,and analyze it correlation with different pathological stagings of gastric cancer.Enzymatic cycling assay was used for detecting serum Hcy.Results:The serum Hcy concentration level in benign disease was (1 2.31 ± 3.22) μ mol/L,and significantly lower than cancer group(1 6.19 ± 4.84) μ mol/L,the difference was statistically significant (P＜0.05):The serum Hcy concentration levels increased gradually from staging I to staging Ⅳ,and the concentration level in staging Ⅰ was (13.94 ± 4.07) μ mol/L,in staging Ⅱ was (15.49 ± 4.09) μ mol/L,in staging Ⅲ was (17.10 ± 4.79) μ mol/L,in stagingⅣ was (19.81 ± 5.77) μ mol/L,the differences among the four groups were statistically significant(P＜0.05).Spearman Rank Correlation analysis confirmed that,the Hcy concentration level was positively related with pathological staging(r=0.503,P＜ 0.001).Logistic regression analysis showed that,the serum Hcy concentration level is significantly correlated with gastric cancer,after the adjustment of other risk factors (OR=1.208,P=0.003).Conclusions:The serum Hcy concentration level is closely correlated with gastric cancer staging,and increase significantly with the cancer staging (from staging Ⅰ to staging Ⅳ),so itcan be used to evaluate the severity of gastric cancer.