Background: In rats, esophagogastroduodenal anastomosis (EGDA) without concomitant chemical carcinogen treatment leads to gastroesophageal reflux disease, multilayered epithelium (MLE, a presumed precursor in intestinal metaplasia), columnar-lined esophagus, dysplasia, and esophageal adenocarcinoma. Previously we have shown that columnar-lined esophagus in EGDA rats resembled human Barrett's esophagus (BE) in its morphology, mucin features and expression of differentiation markers (Lab. Invest. 2004;84:753-765). The purpose of this study was to compare the phenotype of rat MLE with human MLE, in order to gain insight into the nature of MLE and its potential role in the development of BE.

Background: Berberine, a well-known component of the Chinese herbal medicine Huanglian, has wide range of biochemical and pharmacological effects, including antineoplastic effect, but the exact mechanisms remain unclear. The aim of the present study was to evaluate the potential chemo-sensitization effect of berberine in ovarian cancer cell line A2780. Methods: The expression of miR-93 was measure by RT-PCR. The target of miR-93 was confirmed by luciferase activity assay. Hoechst 33258 staining, Annexin V and PI double staining were used for apoptosis analysis. Results: In this study, we found A2780/DDP cells that were incubated with berberine combined with cisplatin had a significantly lower survival than the control group. Berberine enhanced cisplatin induced apoptosis and induced G0/G1 cell cycle arrest in A2780 cells. Next, we observed that the miR-93 levels in cisplatin resistant cell lines were higher than that in cisplatin sensitive cell lines. Furthermore, our study found berberine could inhibit miR-93 expression and function in ovarian cancer, as shown by an increase of its target PTEN, an important tumor suppressor in ovarian cancer. A2780 cells that were treated with PTEN siRNA had increased survival compared to NC group and this could be partly alleviated by the AKT inhibitor Triciribine. More importantly, A2780 cells that were treated with PTEN siRNA had a survival pattern that is similar to cells with miR-93 overexpression. Conclusion: The results suggested that berberine modulated the sensitivity of cisplatin through miR-93/PTEN/AKT signaling pathway in the ovarian cancer cells.

Quaking (QKI) is an alternative splicing factor that can regulate circRNA formation in the progression of epithelialmesenchymal transition, but the mechanism remains unclear. High expression of QKI is correlated with short survival time, metastasis, and high clinical stage and pathology grade in hepatocellular carcinoma (HCC). Here we report that transcription of the QKI gene was activated by the Yin-Yang 1 (YY1)/p65/p300 complex, in which YY1 bound to the superenhancer and promoter of QKI, p65 combined with the promoter, and p300 served as a mediator to maintain the stability of the complex. This YY1/p65/p300 complex increased QKI expression to promote the malignancy of HCC as well as an increased circRNA formation in vitro and in vivo. Hyperoside is one of several plant-derived flavonol glycoside compounds. Through virtual screening and antitumor activity analysis, we found that hyperoside inhibited QKI expression by targeting the YY1/p65/p300 complex. Overall, our study suggests that the regulatory mechanism of QKI depends on the YY1/p65/p300 complex and that it may serve as a potential target for treatment of HCC. Significance: These findings identify the YY1/p65/p300 complex as a regulator of QKI expression, identifying several potential therapeutic targets for the treatment of HCC.

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