This study demonstrates the ability of salinomycin to selectively target "CD133+" cell subpopulations and decrease the malignant traits in colorectal cancer lines.
MicroRNAs (miRNAs) have emerged as critical epigenetic regulators involved in cancer progression. miR-320a has been identified to be a novel tumour suppressive miRNA in colorectal cancer (CRC). However, the detailed molecular mechanisms are not fully understood. Here, we reported that miR-320a inversely associated with CRC aggressiveness in both cell lines and clinical specimens. Functional studies demonstrated that miR-320a significantly decreased the capability of cell migration/invasion and induced G0/G1 growth arrest in vitro and in vivo. Furthermore, Rac1 was identified as one of the direct downstream targets of miR-320a and miR-320a specifically binds to the conserved 8-mer at position 1140-1147 of Rac1 3'-untranslated region to regulate Rac1 protein expression. Over-expression of miR-320a in SW620 cells inhibited Rac1 expression, whereas reduction of miR-320a by anti-miR-320a in SW480 cells enhanced Rac1 expression. Re-expression of Rac1 in the SW620/miR-320a cells restored the cell migration/invasion inhibited by miR-320a, whereas knockdown of Rac1 in the SW480/anti-miR-320a cells repressed these cellular functions elevated by anti-miR-320a. Conclusively, our results demonstrate that miR-320a functions as a tumour-suppressive miRNA through targeting Rac1 in CRC.
Aim: To elucidate the effects of hyperthermic CO 2 pneumoperitoneum on human gastric AGS cells. Methods: Based on a newly devised in vitro study model, we evaluated the anti-cancer effects of HT-CO 2 (42-44˚C for 2-4h) on human gastric cancer cells, and also the corresponding mechanisms. Results: HT-CO 2 (42-44˚C for 2-4h) severely inhibited cell proliferation as assessed by Cell Counting Kit-8 assay, while inducing apoptosis in a temperature-and time-dependent manner demonstrated by annexin-V/PI flow cytometry and morphological analysis (Hoechst/PI fluorescence). In addition, it was found that HT-CO 2 (42-44˚C for 2-4h) promoted the up-regulation of Bax by western blotting. Significantly, it could also suppress gastric cancer cell invasion and metastasis by in vitro invasion and motility assay. Conclusion: In conclusion, HT-CO 2 had an efficacious cytotoxic effect on gastric cancer cells through Bax-induced mitochondrial apoptotic signaling. Our studies indicate that it may serve as a potential therapy for peritoneal carcinomatosis of gastric cancer. Further investigations in vivo using animal models are now urgently needed.
Transmembrane protease/serine 4 (TMPRSS4), a member of the type II transmembrane serine protease family, is highly expressed in some human cancers and involved in the EMT regulation of cancer cells. The prognostic value of TMPRSS4 in colorectal cancer (CRC) has not been discussed. This study aims to evaluate the association between TMPRSS4 expressions and survival in CRC patients. Immunohistochemistry revealed high expression of TMPRSS4 in 69/122 CRC samples, compared with 14/47 in normal tissues (P < 0.01). Correlation analysis showed high expression of TMPRSS4 was significantly associated with advanced TNM stage (P = 0.011), pT (P = 0.019), pN (P = 0.035), and pM status (P = 0.004). Higher TMPRSS4 predicted shorter overall survival (OS) and disease-free survival (DFS) in CRC patients (P < 0.01, both). Moreover, both TMPRSS4 expression and TNM stage were independent predictive factors of OS and DFS in Cox regression analysis. The findings in our study demonstrated the potential value of TMPRSS4 expression level as a prognostic biomarker for CRC patients.
MicroRNAs (miRs) are regulators of the formation and development of hepatocellular carcinoma (HCC). The biological role of miR-4325 in HCC has yet to be determined. This study is aimed at dissecting the role of miR-4325 in HCC and the underlying mechanism. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-4325 expression in HCC tissue specimens and cells. Cell proliferation, migration, and invasion were assessed by using the MTT assay and Transwell assay, respectively. The miR-4325 target was predicted based on bioinformatics analysis and validated using the dual-luciferase reporter assay. Rescue experiments in the cells were utilized to functionally characterize the downstream molecular targets of miR-4325. We observed that miR-4325 expression levels were significantly reduced in both HCC tissue specimens and cell lines. Meanwhile, a lower miR-4325 level was associated with a poorer prognosis. Gain and loss of function assays revealed that miR-4325 markedly downregulated HCC cell growth, migration, and invasion. Moreover, we identified GATA-binding protein 6 (GATA6) as a miR-4325 target and found that GATA6 was abnormally expressed in HCC. Rescue assays demonstrated that the regulatory function of miR-4325 in HCC was mediated by GATA6. Taken together, miR-4325 suppresses HCC cell growth, migration, and invasion by targeting GATA6, suggesting that miR-4325 may potentially serve as a novel therapeutic target for HCC.
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