In this 4T1 murine model of breast cancer, lidocaine decreased pulmonary metastasis when combined with sevoflurane anaesthesia, perhaps via anti-inflammatory and anti-angiogenic effects. It had no such effect in mice given ketamine anaesthesia.
Background
Hepatocellular carcinoma (HCC) is a very belligerent primary liver tumor with high metastatic potential. Aberrant expression of lncRNAs drives tumorous invasion and metastasis. Whether lncRNAs engage mechanisms of liver cancer metastasis remains largely unexplored.
Patients and Methods
We collected HCC tissues from the tumors and their adjacent normal samples in the Chinese population and analyzed the levels of lncRNAs by microarray analysis. The gain- and loss-of-function analysis demonstrated that PCBP1-AS1 accelerated tumorous growth and metastasis in vivo and in vitro. Moreover, we used RNA-pulldown assay to show that PCBP1-AS1 physically interacted with polyC-RNA-binding protein 1 (PCBP1); meanwhile, PCBP1-AS1 was indeed detected in RIP with the PCBP1 antibody. Mechanistically, we first explored the relationship between PCBP1‐AS1 and PCBP1 in HCC cell lines.
Results
Here we show that PCBP1-AS1, identified by microarray analysis on pre- and post-operative HCC plasma specimens, was highly expressed in human HCC, clinically verified as a prometastatic factor and markedly associated with poor prognosis in patients with hepatocellular carcinoma. PCBP1‐AS1 was negatively related with PCBP1 at the messenger RNA and protein expression levels. PCBP1-AS1 triggered PRL-3 and AKT in HCC tumor cells. Additionally, the double knockout of PCBP1 and PCBP1-AS1 abolished the PCBP1-AS1-induced PRL-3-AKT signalling pathway activation.
Conclusion
The upregulation of PCBP1-AS1 enhances proliferation and metastasis in HCC, thus regulating the PCBP1-PRL-3-AKT signalling pathway.
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Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT. RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays revealed that TSA induced an interaction between uc002mbe.2 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in Huh7 cells. This interaction mediated AKT deactivation and p21 induction in liver cancer cells. In an athymic xenograft mouse model, knockdown of uc002mbe.2 significantly prohibited the TSA-mediated reduction in tumor size and weight. In addition, the ability of TSA to reduce hnRNPA2B1 and p-AKT levels and induce p21 in the xenograft tumors was prevented by uc002mbe.2 knockdown. Therefore, the interaction of uc002mbe.2 and hnRNPA2B1 in mediating AKT deactivation and p21 induction is involved in the cytostatic effect of trichostatin in liver cancer cells.
The suppressor of zest 12 (SUZ12), an essential subunit of the transcription polycomb repressive complex 2 (PRC2), has been found to be involved in HBV X-induced oncogenic transformation in hepatocellular carcinoma (HCC). However, the specific function of SUZ12 has not yet been determined in the pathogenesis of migration and invasion of HBV-associated HCC. Here, our results showed that SUZ12 was significantly down-regulated in HBV-related HCC tissues compared with adjacent non-tumor tissues by immunohistochemical and Western blot assays. The 5-years survival rate was worse in patients with low expression level of SUZ12. SUZ12 silencing increased the migration and invasion of HCC cells, and its overexpression impaired HCC cells migration and invasion. Knockdown of SUZ12 activated ERK1/2 pathway and increased MMP9 (matrix metallopeptidase 9) and MMP2 (matrix metallopeptidase 2) expression, whereas SUZ12 overexpression had opposite effects. Specific ERK1/2 inhibitor (SCH772984) significantly decreased HCC cells migration and invasion caused by SUZ12 shRNA. Thus, the liver cancer-down-regulated SUZ12 accelerated the invasion and metastasis of HCC cells. These effects might be associated with deregulation of SUZ12 activating ERK1/2, MMP2 and MMP9 in HCC cells.
Introduction. Considering the narrow window of surgery, early diagnosis of liver cancer is still a fundamental issue to explore. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA) are considered as two different types of liver cancer because of their distinct pathogenesis, pathological features, prognosis, and responses to adjuvant therapies. Qualitative analysis of image is not enough to make a discrimination of liver cancer, especially early-stage HCC or ICCA. Methods. This retrospective study developed a radiomic-based model in a training cohort of 122 patients. Radiomic features were extracted from computed tomography (CT) scans. Feature selection was operated with the least absolute shrinkage and operator (LASSO) logistic method. The support vector machine (SVM) was selected to build a model. An internal validation was conducted in 89 patients. Results. In the training set, the AUC of the evaluation of the radiomics was 0.855 higher than for radiologists at 0.689. In the valuation cohorts, the AUC of the evaluation was 0.847 and the validation was 0.659, which indicated that the established model has a significantly better performance in distinguishing the HCC from ICCA. Conclusion. We developed a radiomic diagnosis model based on CT image that can quickly distinguish HCC from ICCA, which may facilitate the differential diagnosis of HCC and ICCA in the future.
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