Increasing evidence has indicated that dysregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including HCC. Previous studies have shown that the lncRNA AFAP1-AS1 plays a critical role in cancer. However, the roles of AFAP1-AS1 in HCC remain to be determined. In the present study, AFAP1-AS1 was found to be increased in HCC tissues, and high AFAP1-AS1 expression was associated with tumor size, TNM stage, vascular invasion, and poor prognosis. Silencing of AFAP1-AS1 significantly reduced cell proliferation, clonal growth, cell migration, and invasion and increased apoptosis in vitro. Furthermore, AFAP1-AS1 silencing markedly reduced tumor growth in a murine allograft model in vivo. The results suggested that AFAP1-AS1 is important in HCC development and serves as a therapeutic target of HCC.

BackgroundHepatocellular carcinoma (HCC) is one of the most frequent cancers in the world. Calreticulin(CRT) is aberrantly overexpressed in many human cancer cells. The function of CRT in HCC cells remains unclear. We attempted to investigate the effects and the underlying mechanisms of CRT down-regulation on HCC cell growth, apoptosis, cell cycle progression and invasion.MethodsTo investigate the function of CRT in HCC cells, small interfering RNA (siRNA) was used to knock down the expression of CRT in SMMC7721 and HepG2 HCC cells. CRT expression was examined by Western blot and immunofluorescence. Cell proliferation was detected by CCK-8 assay. Cell cycle and apoptosis were measured by the flow cytometry. The invasion capability was assessed by transwell assay. The phosphorylation level of Akt was evaluated by Western blot.ResultsCompared with human hepatic cells L02, CRT was apparently up-regulated in SMMC7721, HepG2 and Huh7 HCC cells. Down-regulation of CRT expression effectively inhibited HCC cell growth and invasion. CRT knockdown induced cell cycle arrest and the apoptosis in SMMC7721 and HepG2 cells. Furthermore, down-regulation of CRT expression significantly decreased the Akt phosphorylation.ConclusionsCRT was aberrantly over-expressed in HCC cell lines. CRT over-expression contributes greatly to HCC malignant behavior, likely via PI3K/Akt pathway. CRT could serve as a potential biomarker and therapeutic target for hepatocellular carcinoma.

Purpose: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML.Experimental Design: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model.Results: Six flow cytometry-validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P < 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P < 0.001), 44% versus 18% (P ¼ 0.041), 44% versus 24% (P ¼ 0.004), and 62% versus 32% (P < 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P ¼ 0.005), 2.12 (P ¼ 0.004), 2.02 (P ¼ 0.034), 1.66 (P ¼ 0.019), and 1.59 (P ¼ 0.001) in the training and validation cohorts, respectively.Conclusions: Our immune risk score complements current AML prediction models.

Background: E2F2 is a member of the E2F transcription factor family and has important but not fully understood biological functions in cancers. The biological role of E2F2 in gastric cancer (GC) also remains unclear. Methods: We examined the expression levels of E2F2 in GC using publicly available datasets such as TIMER, Oncomine, GEPIA, UALCAN, etc., and in our patient cohort, using quantitative real-time PCR, western blotting, and immunohistochemistry. We further investigated the effects of E2F2 on phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling, autophagy, and the migration and invasion of GC cells by the wound healing assay, Transwell assay and transmission electron microscopy. Results: E2F2 was highly expressed in both GC tissues and cells compared with normal gastric tissues/cells. High E2F2 expression was associated with poor overall survival (OS). In addition, the expression of E2F2 in GC was strongly correlated with a variety of immune markers. E2F2 overexpression promoted the migration and invasiveness of GC cells in vitro through inhibition of PI3K/Akt/mTOR-mediated autophagy. Conclusion: High E2F2 expression was associated with the characteristics of invasive tumors and poor prognosis. E2F2 also had potential modulatory effects on tumor immunity. We discovered a novel function of E2F2 in the regulation of PI3K/Akt/mTOR-mediated autophagy and the downstream processes of cell migration and invasion.

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