Objectives To determine whether the upregulation of basic leucine zipper ATF-like transcription factor 2 (BATF2) by calycosin suppresses the growth and epithelial-to-mesenchymal transition (EMT) in human colorectal cancer (CRC) cells. Method Cells were cultured and treated with different concentrations of calycosin for different periods of time. Protein and mRNA expression was determined by western blotting and quantitative PCR. Cell migration was assessed by Transwell experiments. Co-immunoprecipitation and luciferase assays were used to analyze the association between BATF2 and plasminogen activator inhibitor-1. (PAI-1). Cell apoptosis was determined by flow cytometry; β-catenin cellular localization was visualized by immunofluorescent staining. Results Calycosin up-regulated the expression of BATF2 via the signal transducer and activator of transcription 3 (STAT3) pathway, which was antagonized by transforming growth factor beta (TGF-β), calycosin promoted the cell apoptosis and growth inhibition via phosphoinositide 3-kinase (PI3K)/Akt pathway. TGF-β promoted cell growth, which was inhibited by calycosin regulating the expression of proliferating cell nuclear antigen (PCNA) via the phosphoinositide 3-kinase pathway. TGF-β suppressed expression of BAX via the phosphoinositide 3-kinase pathway but induced cell apoptosis .calycosin enhanced the effect of TGF-β on cell apoptosis,In addition, calycosin suppressed TGF-β-induced cell migration by increasing BATF2 to target PAI-1. TGF-β-induced EMT was inhibited by calycosin in human CRC LoVo and HCT116 cell lines via the Wnt signaling pathway. Conclusions The induction of BATF2 by calycosin may be a feasible therapeutic option for CRC. Graphical Abstract .

Background:Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is a 1752-bp lncRNA transcribed from m8q24 genomic region. A lot of investigations have confirmed the involvement of CCAT2 in the tumorigenesis of many cancer types. Previous studies found that over-expression of CCAT2 significantly promoted cell migration and proliferation, and inhibited apoptosis of HCC cells. In the present investigation, the clinical value and prognostic significance of CCAT2 were investigated.Methods:The 122 pairs of HCC tissues and adjacent normal liver tissues were acquired between September 2013 and February 2018. The expression levels of CCAT2 in HCC tissues and their corresponding adjacent normal liver tissues were examined by RT-qPCR analysis. Survival was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent prognostic indicators were determined in the multivariate analysis using Cox's proportional hazard model.Results:CCAT2 expression levels were significantly increased in HCC tissues compared to that in their normal counterparts (P < .001). CCAT2 expression was significantly correlated with vascular invasion (P = .001), histopathologic grading (P = .001), distant metastasis (P = .002) and TNM stage (P = .018). A Kaplan–Meier survival curve showed that the overall survival rate of HCC patients in high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = .016). In addition, COX multivariate analysis showed that high expression of CCAT2 was an independent risk factor for predicting shorter overall survival time in HCC (HR = 2.126, 95%CI:1.273–8.775, P = .021).Conclusions:Taken together, this research revealed that lncRNA CCAT2 may serve as a potential biomarker for predicting overall survival time in HCC.

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