PurposeStudies 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 MethodslncRNA-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.ResultsIn 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.ConclusionThis 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.
Background: Studies evaluating the prognostic significance of programmed death-ligand 1 (PD-L1) expression in colorectal cancer (CRC) are limited and remain controversial. This meta-analysis was conducted in order to evaluate the clinicopathological and prognostic significance of PD-L1 expression in CRC patients. Methods: A comprehensive search was performed against the Medline/PubMed, Embase, Cochrane Library, Web of Science (WoS) and Scopus databases. Data were extracted with name of the first author, year of publication, country of origin, tumor type, number of cases, staining method, cut-off values, PD-L1 positive expression, clinicopathological parameters, outcome, and quality assessment score, and statistical analysis was conducted using Review Manager Version 5.3 (Revman the Cochrane Collaboration; Oxford, England) and STATA version 14 (Stata Corporation; College Station, TX, USA). Results: Ten studies were included in this meta-analysis, in which the pooled hazard ratio (HR) showed that PD-L1 expression in tumor cells was significantly associated with a poor overall survival (HR = 1.50, 95% CI 1.05–2.13, P = 0.03). The pooled HR for disease-free survival (DFS) indicated that PD-L1 expression was significantly associated with shorter DFS (HR = 2.57, 95% CI 1.40–4.75, P = 0.002). The pooled odds ratios (ORs) showed that PD-L1 expression was associated with poor differentiation (OR = 3.47, 95% CI 1.37–8.77, P = 0.008) and right colon cancer (OR = 2.38, 95% CI 1.57–3.60, P < 0.0001). However, the expression of PD-L1 was independent of gender, age, tumor size, tumor stage, lymph node metastasis, and tumor-node metastasis stage. Conclusion: This meta-analysis indicated that a high level of PD-L1 expression might be a biomarker for a poor prognosis in CRC patients. This information may be helpful for clinicians to stratify CRC patients for anti-PD-1/PD-L1 therapy, particularly patients with microsatellite instability high (MSI-H).
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