Song and Luo review the roles of post-translational modifications in ubiquitin signaling.

Lung carcinoma is the most common human cancer with poor prognosis and has an increasing incidence in recent years. However, the related mechanism of lung cancer onset has not been completely explored. Piwi-interacting RNA (piRNA) is a type of noncoding small RNA with established function in germ cells, and interestingly, piRNA has also been shown to be implicated in cancer biology. In this study, piR-55490 was found to be silenced in lung carcinoma specimens and cell lines, compared with normal lung tissues and cells. Intriguingly, the expression level of piR-55490 is negatively associated with patients' survival. Restoration of piR-55490 can reduce the proliferation rates of lung cancer cells, while piR-55490 suppression led to the gain in the proliferation rates. Animal model study showed that piR-55490 can suppress the growth of lung carcinoma xenograft. Further study revealed that piR-55490 suppressed the activation of Akt/mTOR pathway in lung cancer cells. Surprisingly, piR-55490 was found to bind 3'UTR of mTOR messenger RNA (mRNA) and induce its degradation in a mechanism similar to microRNA (miRNA). The introduction of an mTOR construct resistant to action of piR-55490 was able to abolish the effect of piR-55490 on lung cancer cells. In conclusions, we found that piRNA can contribute to the suppression of cancer cell phenotypes by directly targeting a oncogene mRNA. This finding facilitates our understanding of piRNA's function and its association with human cancer.

6′-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from peony root, has been proven to possess antioxidant potential. In this present study, we revealed that GPF treatment exerted significant neuroprotection of PC12 cells following OGD, as evidenced by a reduction of oxidative stress, inflammatory response, cellular injury, and apoptosis in vitro. Furthermore, treatment with GPF increased the levels of phosphorylated Akt (p-Akt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as promoted Nrf2 translocation in PC12 cells, which could be inhibited by Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K). In addition, Nrf2 knockdown or Ly294002 treatment significantly attenuated the antioxidant, anti-inflammatory, and antiapoptotic activities of GPF in vitro. In vivo studies indicated that GPF treatment significantly reduced infarct volume and improved neurological deficits in rats subjected to CIRI, as well as decreased oxidative stress, inflammation, and apoptosis, which could be inhibited by administration of Ly294002. In conclusion, these results revealed that GPF possesses neuroprotective effects against oxidative stress, inflammation, and apoptosis after ischemia-reperfusion insult via activation of the PI3K/Akt/Nrf2 pathway.

ObjectiveTo investigate the effects of microRNA-7 (miR-7) on the proliferation, migration and invasion of non-small cell lung cancer NSCLC) cells by targeting FAK through ERK/MAPK signaling pathway.MethodsNSCLC tissues and adjacent normal tissues were obtained from 160 NSCLC patients after operation. NSCLC cell lines (A549, H1299 and H1355) and a normal human fetal lung fibroblast cell line (MRC-5) were obtained. NSCLC cells were assigned into miR-7 inhibitors, miR-7 mimics, blank, miR-7 mimics control, miR-7 inhibitors control, FAK siRNA and miR-7 inhibitors + FAK siRNA groups. The expressions of miR-7 and FAK mRNA in tissues and cell lines were detected by qRT-PCR and Western-Blotting. Cell proliferation, migration and invasion were detected by MTT assay, wound scratch assay and Transwell assay.ResultsCompared with adjacent normal tissues, miR-7 expression was down-regulated, but the mRNA and protein expressions of FAK, ERK and MAPK were up-regulated. Compared with the blank and mimics control groups, miR-7 significantly increased but FAK, ERK and MAPK expressions decreased in miR-7 mimics and FAK siRNA groups. Cell proliferation, migration and invasion were inhibited in the miR-7 mimics and FAK siRNA groups, while opposite regarding miR-7 inhibitors group.ConclusionThe miR-7 can inhibit the activation of ERK/MAPK signaling pathway by down-regulating FAK expression, thereby suppressing the proliferation, migration and invasion of NSCLC cells. The miR-7 and its target gene FAK may be novel targets for the diagnosis and treatment of NSCLC.

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Background/Aim: Crocetin is a readily bioavailable and bioactive compound extracted from Saffron. Previous studies indicated its various biomedical properties including antioxidant and anti-coagulation potencies. However, its effect on inflammation, notably within the cardiovascular system, has not been investigated yet. In the present study, we utilized human umbilical vein endothelial cell (HUVEC) to elucidate the effect of Crocetin on vascular inflammation. Methods: Cell viability and toxicity were evaluated by MTT and Lactate dehydrogenase (LDH) assay, respectively. Pro-inflammatory chemokine Monocyte Chemoattractant Protein-1 (MCP-1) and Interleukin-8 (IL-8) expressions were determined by RT-PCR and ELISA. With fluorescence labeled U937 cells, we examined immune cell adhesion to the inflamed HUVEC in vitro, which was further confirmed by the H&E staining in the murine subcutaneous endothelium in vivo. Results: Upon Lipopolysaccharide (LPS)-induced inflammatory response in HUVECs, Crocetin ameliorated cell cytotoxicity, suppressed MCP-1 and IL-8 expressions through blocking NF-κB p65 signaling transduction. Moreover, Crocetin inhibited immune cells adhesion and infiltration to inflamed endothelium, which is a key step in inflammatory vascular injury. Conclusions: These findings suggest that Crocetin, a natural herb extract, is a potent suppressor of vascular endothelial inflammation.

This study aimed to explore the effects of miR-21 and PTEN/Akt signaling pathway on TGF-β1-induced epithelial-mesenchymal transition (EMT) in gastric cancer (GC). GC tissues and adjacent tissues were collected from 83 patients. The qRT-PCR assay was performed to detect miR-21 expression. The expressions of PTEN, Akt and p-Akt were detected by immunohistochemistry. After 48 h of treatment with TGF-β1 (10 ng/mL), the SGC-7901 and KATO-III cells were divided into the blank, negative control (NC), miR-21 inhibitors, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups. EMT related factors and PTEN expressions were detected by qRT-PCR assay and Western blotting. The scratch test was conducted to observe cell migration. Xenograft tumor model in nude mice was used to evaluate the effects of miR-21 on EMT of GC cells in vivo. In GC tissues, the expressions of miR-21, Akt and p-Akt were up-regulated, while PTEN expression was down-regulated. Gene and protein expressions of E-cadherin and PTEN in the miR-21 inhibitors group were higher than the blank, NC, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups, while the expressions of N-cadherin, β-catenin, Vimentin and Slug in the miR-21 inhibitors group were lower than other groups. MiR-21 inhibitors significantly inhibit cell migration and invasion in GC cell lines. In vivo xenograft experiment revealed that miR-21 inhibitor inhibits the growth of transplanted tumor through up-regulating E-cadherin and PTEN expressions and down-regulating the expressions of N-cadherin, β-catenin, Vimentin and Slug. These results suggest that miR-21 could promote TGF-β1-induced EMT in GC cells through up-regulating PTEN expression.

MicroRNAs (miRNAs or miRs) regulate gene expression at the posttranscriptional level and are involved in many biological processes such as cell proliferation and migration, stem cell differentiation, inflammation, and apoptosis. In particular, miR-144-3p is downregulated in various cancers, and its overexpression inhibits the proliferation and metastasis of cancer cells. However, the role of miR-144-5p in non-small-cell lung cancer (NSCLC), especially radiosensitivity, is unknown. In this study, we found that miR-144-5p was downregulated in NSCLC clinical specimens as well as NSCLC cell lines exposed to radiation. Enhanced expression of miR-144-5p promoted the radiosensitivity of NSCLC cells in vitro and A549 cell mouse xenografts in vivo. Furthermore, we identified activating transcription factor 2 (ATF2) as the direct and functional target of miR-144-5p using integrated bioinformatics analysis and a luciferase reporter assay. In addition, restoration of ATF2 expression inhibited miR-144-5p-induced NSCLC cell sensitivity to radiation in vitro and in vivo. Our findings suggest that deregulation of the miR-144-5p/ATF2 axis plays an important role in NSCLC cell radiosensitivity, thus representing a new potential therapeutic target for NSCLC.