Metastasis is one of the main causes of death in patients with colorectal cancer (CRC). Brg-1 is a central component of the SWItch/Sucrose NonFermentable chromatin-remodeling complex, which features a bromodomain and helicase/ATPase activity. The gene encoding Brg-1 is frequently mutated or silenced in human cancers. Several reports have proposed Brg-1 as a tumor suppressor; however, little is known about its role in oncogenesis and metastasis. Here we demonstrated that decreased Brg-1 regulates a novel miR-550a-5p/RNF43/Wnt/β-catenin signaling pathway, to promote CRC metastasis in vitro and in vivo. In particular, we used high-throughput RNA-sequencing analysis to show that Brg-1 negatively regulates miR-550a-5p in CRC cells. We further found that Brg-1 inhibits the transcriptional activity of miR-550a-5p promoter, and that decreased Brg-1 expression increased miR-550a-5p expression. We also identified ring finger 43 (RNF43), an inhibitor of Wnt/β-catenin signaling, as a target of miR-550a-5p. Knockdown of Brg-1 by small interfering RNA led to decreased RNF43 expression, increased Wnt signaling and increased CRC cell migration and invasion. This novel pathway defines a new function for Brg-1 and provides potential targets for the treatment of Brg-1 mutant and loss-of-function tumors.
MicroRNAs are a class of small non-coding RNAs that regulate the expressions of many genes. Previously, we found that the expression of p55PIK, an isoform of phosphatidylinosotol 3-kinase that has important roles in the regulation of cell cycle, is increased significantly in several types of cancer and contributes to the tumor growth. However, the mechanism for this increased p55PIK expression is not well understood. In this study, we show that miR-148b binds specifically to the 3'-untranslated region of p55PIK and significantly suppresses p55PIK expression. MiR-148b overexpression abolished p55PIK stimulation of cell proliferation and cell cycle progression in colorectal cancer (CRC) cell lines and decreased tumor growth in vivo. Furthermore, we demonstrated that p53 directly activates the transcription of miR-148b by binding to its promoter. In CRC cell lines and tissues, p53 expression was associated with miR-148b expression, and both were negatively associated with p55PIK expression. Our study shows that the p53/miR-148b/p55PIK axis has an important role in cell proliferation and tumor growth, and may represent a novel therapeutic target for treating cancers containing p53 mutations or losses.
CEA protein and mRNA levels in peritoneal lavage show a high diagnostic accuracy and may help accurately predict the peritoneal recurrence after curative resection of gastric cancer.
ObjectiveXiaoaiping (XAP) is a traditional Chinese medicine that is a commonly used as an anticancer drug in clinical practice owing to its high efficiency and low toxicity. Specifically, XAP can effectively inhibit the growth of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a key HCC diagnostic marker and is closely related to certain malignant cytological behaviors of HCC. However, whether AFP expression and XAP treatment are related to the invasion and metastasis of HCC remains unclear. In the present study, we aimed to evaluate the effects and underlying mechanism of XAP on the invasion and metastasis of HCC..MethodsUsing a cell scratch assay, Transwell technology, and western blotting we detected the different invasion and metastatic abilities of Hep3B cells in XAP treatment and blank control groups. This allowed comparison of the invasion and metastatic abilities of Hep3B cells with differing levels of AFP expression. AFP mRNA sequencing technology was used to analyze the mechanism of tumor invasion and metastasis associated with AFP and XAP treatment.ResultsCell invasion and metastasis abilities in the XAP group were significantly lower than those in the control group (P < 0.05). Additionally, compared to the control group, the expression of AFP significantly decreased after XAP treatment (P < 0.05). The ability of Hep3B cells to invade and metastasize was promoted when AFP expression was up-regulated, whereas it was inhibited when AFP was silenced. XAP injection and AFP regulate the invasion and metastatic ability of HCC by affecting matrix metalloproteinases(MMPs).ConclusionXAP injection inhibits the invasion and metastatic ability of HCC by influencing the expression of AFP; additionally, this inhibition of AFP is achieved by affecting MMPs.
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