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BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies around the world. It has been verified that the expression of SOX18 is correlated to poor clinical prognosis in patients with ovarian cancer, non-small cell lung cancer, or breast invasive ductal carcinoma. However, the expression pattern and biological function of SOX18 in HCC tissues remains unclear. In this study, we set out to investigate the associated biological function and potential molecular mechanism of the SOX18 gene in HCC cells. MATERIAL AND METHODS The mRNA and protein expression levels of experimental related genes were detected by real-time polymerase chain reaction and western blotting assay, respectively. The MTT method was used to assess cell viability, and cell apoptosis analysis was performed by means of FACScan flow cytometry. Wound-healing assay and Transwell analysis were performed to evaluate the ability of cell migration and invasiveness, respectively. RESULTS SOX18 was highly expressed in various HCC cell lines. In addition, SOX18 promoted cell viability, migration, and invasion and simultaneously induce cell apoptosis. SOX18 promoted epithelial-to-mesenchymal transition (EMT) progression, and SOX18 downregulation activated the autophagy signaling pathway AMPK/mTOR in HCC cells. CONCLUSIONS SOX18 downregulation in HCC cells suppressed cell viability and metastasis, induced cell apoptosis and hindered the occurrence and progression of tumor cells by participating in the EMT process and regulating the autophagy signaling pathway AMPK/mTOR.

Non-small-cell lung cancer (NSCLC) is one of the most frequent solid tumors and regarded as a significant threat to individual health around the world. MicroRNAs (miRs) are recognized as critical governors of gene expression during carcinogenesis, while their clinical significance and mechanism in NSCLC occurrence and development are required for further investigation. In this report, we characterized the functional role of miR-598 and its regulation mechanism in NSCLC. The expression level of miR-598 in NSCLC tissues and cell lines was detected by qRT-PCR. A549 cells were transiently transfected with miR-598 mimics or miR-598 inhibitors. Scratch assay and Transwell assay were used to detect cell transfection, migration, and invasion. Possible binding sites of miR-598 in MSI2 mRNA were predicted by bioinformatics and validated by dual-luciferase reporter gene system. The ability of migration and invasion was examined on cells transfected with MSI2 alone or cotransfected A549 cells with miR-598. The expression of miR-598 in NSCLC tissues was significantly lower than that in adjacent tissues, and the expression of miR-598 in NSCLC cell lines (A549, H1650, and H1299) was also significantly lower than that of normal lung epithelial cell line BEAS-2B. A549 cells were significantly inhibited in migration and invasion after transfection with miR-598 mimics, while miR-598 inhibitors were significantly enhanced in migration and invasion. MSI2 was a direct target gene of miR-598. MSI2 can promote the migration and invasion of A549 cells, but the ability to promote cell migration and invasion was reversed when miR-598 was introduced. In conclusion, miR-598 inhibits the migration and invasion of NSCLC by downregulating the target gene MSI2.

Mertk belongs to the Tyro3, Axl and Mertk (TAM) family of receptor tyrosine kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement during phagocytosis. Phagocytosis by either professional or non-professional phagocytes is impaired in the Mertk deficient individual. In the present study, we further investigated the effects of Mertk mutation on peritoneal macrophage morphology, attachment, spreading and movement. Mertk-mutated macrophages exhibited decreased attachment, weak spreading, loss of spindle-like body shape and lack of clear leading and trailing edges within the first few hours of culture, as observed by environmental scanning electron microscopy. Time-lapse video photography recording showed that macrophage without Mertk conducted mainly random movement with oscillating swing around the cell body, and lost the directional migration action seen on the WT cells. Western blotting showed a decreased phosphorylation of focal adhesion kinase (FAK). Immunocytochemistry revealed that actin filaments and dynamic protein myosin II failed to concentrate in the leading edge of migrating cells. Microtubules were localized mainly in one side of mutant cell body, with no clear MTOC and associated radially-distributed microtubule bundles, which were clearly evident in the WT cells. Our results suggest that Mertk deficiency affects not only phagocytosis but also cell shape and migration, likely through a common regulatory mechanism on cytoskeletons.

The corneal epithelium protects the eye from environmental injury. Cornea-related diseases are the second major cause of blindness after cataract. Loss of vision occurs primarily from corneal scarring and vascularization.1 Vitamin A deficiency causes xerophthalmia, which is still a leading cause of childhood blindness due to corneal opacity associated with neovascularization. Because the corneal epithelium completely turns over every 7 to 10 days, there is ongoing corneal epithelial differentiation from proliferative progenitor cells scattered throughout the corneal epithelium and from the stem cells concentrated in the limbal region.2–4 Progenitor cells in the basal layer divide and migrate gradually to the upper epithelial layer. During this process, the cells switch expression of cytokeratins from the progenitor markers keratin-5 (K5) and -14 (K14) to the differentiation-specific isoforms keratin-3 (K3) and -12 (K12).5 The differentiated cells in the superficial layer then form tight junctions, which function as a barrier to protect the cornea.6,7 After injury, the corneal epithelium is rapidly repopulated via a wound-healing process involving mobilization of the corneal stem cells. This wound-healing process is composed of three sequential and partially overlapping steps including cell migration, proliferation, and differentiation.8,9 14-3-3σ is essential for skin epithelial differentiation,10,11 as demonstrated by the studies on the repeated epilation (Er) mouse that carries a null mutation in 14-3-3σ. 14-3-3σ is unique among seven 14-3-3 isoforms, which act exclusively as homodimers and are able to suppress tumor formation, and its expression is restricted to stratified squamous epithelial cells. It is induced at the transition from basal progenitor cells to suprabasal cells during the epidermal keratinocyte differentiation.10,12 14-3-3σ expression has been confined to corneal and conjunctival epithelial cells in humans and is secreted into the culture medium from either primary cells or cell lines.13 In this report, we show that mice mutant for both copies of 14-3-3σ are defective in embryonic corneal development. Although the heterozygous mice exhibit normal corneal development and epithelial homeostasis during embryonic and early postnatal development, they develop an age-dependent corneal plaque formation associated with corneal epithelial wound-healing dysfunction and meibomian gland atrophy.