Hepatic fibrosis is a physiological response to liver injury that includes a range of cell types. The pathogenesis of hepatic fibrosis currently focuses on hepatic stellate cell (HSC) activation into muscle fiber cells and fibroblasts. Baicalin is a flavone glycoside. It is the glucuronide of baicalein, which is extracted from the dried roots of Scutellaria baicalensis Georgi. Previous work focused on the anti-viral, -inflammatory and -tumor properties of baicalin. However, the potential anti-fibrotic effects and mechanisms of baicalin are not known. The present study demonstrated that baicalin influenced the activation, proliferation, apoptosis, invasion and migration of platelet-derived growth factor-BB-induced activated HSC-T6 cells in a dose-dependent manner. To investigate the anti-fibrotic effect of baicalin, a one-color micro (mi)RNA array and reverse transcription-quantitative polymerase chain reaction analyses were used. Results demonstrated that baicalin increased the expression of the miRNA, miR-3595. In addition, the inhibition of miR-3595 substantially reversed the anti-fibrotic effect of baicalin. The present data also suggested that miR-3595 negatively regulates the long-chain-fatty-acid-CoA ligase 4 (ACSL4). Furthermore, ACSL4 acted in a baicalin-dependent manner to exhibit anti-fibrotic effects. Taken together, it was concluded that baicalin induces miR-3595 expression that modulates the expression levels of ACSL4. To the best of our knowledge, the present study is the first to demonstrate that baicalin induces overexpression of human miR-3595, and subsequently decreases the expression of ACSL4, resulting in an anti-fibrotic effect.

CD24 is a glycosylphosphatidylinositol-anchored membrane protein reported to be overexpressed in human tumorigenesis and progression. Our purpose was to determine the role of CD24 in the proliferation of colorectal cancer cells and the potential mechanisms in this process. Our data showed that CD24 promoted cell growth and induced activation of extracellular signal-regulated kinases, Raf-1, and p38 mitogen-activated protein kinase. Furthermore, suppression of extracellular signal-regulated kinases and p38 mitogen-activated protein kinase activity by their specific inhibitors, U0126 and SB203580, abrogated CD24-induced proliferation in vitro. By tumorigenicity assay in female BALB ⁄ c nude mice, we further demonstrated that CD24 promoted tumor growth in vivo. Immunohistochemical analysis revealed that CD24 expression occurred in 92.5% of human colorectal cancer tissue, and increased with tumor progression. More importantly, the stainings of phospho-extracellular signal-regulated kinases and phosphop38 mitogen-activated protein kinase were strongly correlated with CD24 expression. Taken together, our data suggest that CD24-dependent extracellular signal-regulated kinases and p38 mitogen-activated protein kinase activations are required for colorectal cancer cell proliferation in vitro and in vivo. The linkage of CD24 and the mitogen-activated protein kinase pathway may unravel a novel mechanism in the regulation of colorectal cancer

P21-activated protein kinase1 (PAK1), a main downstream effector of small Rho GTPases, Rac1, and Cdc42, plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis. Despite its importance, the molecular mechanisms of PAK1 that contributed to colorectal carcinogenesis remain unclear. Our immunohistochemistry showed that PAK1 expression was increased with colorectal cancer (CRC) progression through the adenoma to carcinoma sequence. Furthermore, our results suggested a relationship between PAK1 nuclear localization and the Dukes staging. In the present study, we showed that PAK1 knockdown decreased proliferation and delayed the G1/S cell-cycle transition, and increased apoptosis in vivo and in vitro. In addition, PAK1 knock-down downregulated c-Jun amino terminal kinases (JNK) activity and the levels of cyclinD1, CDK4/6. Inhibition of the JNK activity by chemical inhibitor (SP600125) significantly reduced the effects of PAK1 on CRC proliferation via accumulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). In conclusion, our results demonstrate that knockdown of PAK1 could enhance the chemosensitivity of CRCs to 5-fluorouracil through G1 arrest. The mechanism by which PAK1 induced cancer growth might involve activation of JNK as well as downregulation of PTEN. Targeting PAK1 may represent a novel treatment strategy for developing novel chemotherapeutic agents.