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Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) is one kind of cytoplasmic long non-coding RNA (lncRNA), which has been demonstrated to play a critical function in multiple cancers. However, the detailed mechanism of OIP5-AS1 in the regulation of cervical cancer progression is still obscure. Here, we demonstrated that lncRNA OIP5-AS1 was upregulated in cervical cancer and was correlated with poor prognosis by bioinformatics studies. OIP5-AS1 depletion inhibited cell proliferation and promoted cell apoptosis in cervical cancer cells. Furthermore, we clarified that ROCK1 was the downstream effector of OIP5-AS1 and OIP5-AS1 acted as a molecular sponge of miR-143-3p. Finally, we verified that OIP5-AS1 exerted its function in the regulation of cervical cancer progression via interacting with miR-143-3p to regulate ROCK1 expression. Our study revealed novel mechanisms about how lncRNA OIP5-AS1 executed its function in cervical cancer and thus provided potential therapeutic targets for the disease.

Porcine reproductive and respiratory syndrome virus(PRRSV) is an important immunosuppressive virus which can suppresses infected cells proliferation. In this work, we examined PRRSV ability to manipulate cell cycle progression of MARC-145 cells and explored the potential molecular mechanisms. The results showed that PRRSV infection imposed a growth-inhibitory effect on MARC-145 cells by inducing cell cycle arrest at G2/M phase. This arrest was due to the significant decrease of Cdc2-cyclinB1 complex activity in PRRSV-infected cells and the activity reduction was a result of Cdc2 Tyr15 phosphorylation and the accumulation of Cdc2 and cyclinB1 in the nucleus. Not only elevated Wee1 and Myt1 expression and inactivated Cdc25C, but also increase of p21 and 14-3-3σ in a p53-dependent manner caused the inhibitory Tyr15 phosphorylation of Cdc2. PRRSV infection also activated Chk1. Our data suggest PRRSV infection induces G2/M arrest via various molecular regulatory mechanisms. These results provide a new insights for PRRSV pathogenesis.

Red raspberry contains a variety of bioactive ingredients and has high edible and medicinal value. Red raspberry extractions (RREs) have strong antioxidant capacity and anticancer ability in vivo and in vitro. This study was to explore the specific mechanism of RREs inhibiting the proliferation of liver cancer HepG2 cells and provide a theoretical basis for the prevention and treatment of liver cancer by RREs. HepG2 cells were cultured in vitro, and MTT assay was adopted to detect the effect of RREs on HepG2 cell activity. Colony formation assay was applied to detect the growth and proliferation of cells, cell apoptosis was detected by flow cytometry, and dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was adopted to detect the effect of RREs on the production of reactive oxygen species (ROS) in cells. The effect of RREs on cell mitochondrial membrane potential was evaluated by mitochondrial membrane potential assay kit with JC-1 (JC-1 assay), and western blot was used to detect the expression of apoptosis-related proteins (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax), and Caspase-3), thus investigating the effect of RREs on the molecular mechanism of HepG2 cell apoptosis. The results showed that RREs could inhibit the proliferation activity of HepG2 cells and promote their apoptosis in a concentration-dependent manner. The level of ROS in HepG2 cells interfered by RREs increased markedly, while the cell mitochondrial membrane potential decreased sharply. As the concentration of HepG2 increased, the mitochondrial membrane potential reduced steeply. Western blot results showed that the expression of apoptosis-related protein Bcl-2 in the RREs treatment group dropped, but the expression of Bax and Caspase-3 rose. In summary, RREs could inhibit the proliferation of liver cancer HepG2 cells and promote their apoptosis. This inhibition might be executed by inducing HepG2 cells to produce ROS, a decrease in Bcl-2/Bax protein ratio, and an obvious reduction in mitochondrial membrane potential. [ABSTRACT FROM AUTHOR]

The inhibition of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal protein kinase (JNK), p38 MAPK (p38) and extracellular signal-regulated protein kinase 1/2 (ERK1/2), have an important effect on lung ischemia-reperfusion injury (IRI) during lung transplantation (LT). However, the way in which combined MAPK inhibition exerts optimal protective effects on lung IRI remains to be elucidated. Therefore, the present study evaluated the therapeutic efficacy of the inhibition of MAPKs in rat pulmonary microvascular endothelial cells (PMVECs) in an IRI model of LT. The rat PMVECs were transfected with small interfering RNAs (siRNAs) against JNK, p38 or ERK1/2. Cotransfection was performed with siRNAs against JNK and p38 in the J+p group, JNK and ERK1/2 in the J+E group, p38 and ERK1/2 in the p+E group, or all three in the J+p+E group. Non-targeting (NT) siRNA was used as a control. The PMVECs were then treated to induce IRI, and the levels of inflammation, apoptosis and oxidative stress were detected. Differences between compared groups were determined using Tukey's honest significant difference test. In all groups, silencing of the MAPKs was shown to attenuate inflammation, apoptosis and oxidative stress to differing extents, compared with the NT group. The J+p and J+p+E groups showed lower levels of interleukin (IL)-1ß, IL-6 and malondialdehyde, a lower percentage of early-apoptotic cells, and higher superoxide dismutase (SOD) activity, compared with the other groups. No significant differences were observed in the inflammatory response, SOD activity or early apoptosis between the J+p and J+p+E groups. These findings suggested that the dual inhibition of JNK and p38 led to maximal amelioration of lung IRI in the PMVECs of the IRI model of LT, which occurred through anti-inflammatory, anti-oxidative and anti-apoptotic mechanisms. [ABSTRACT FROM AUTHOR]

Background Lung ischemia-reperfusion injury (LIRI) is a pathologic process that is observed in several clinical conditions, and p38 mitogen-activated protein kinase (MAPK) is involved. Diabetes mellitus (DM) results in an increased incidence of ischemia-induced organ damage. The aims of this study were to examine the effects of DM on LIRI in a rat model of DM and to explore the possible mechanisms in relation to the p38 MAPK pathway. Methods Forty rats were randomly divided into the following five groups ( n = 8 each): a control + sham group, a control + IR group (CIR), a DM + sham group, a DM + IR group (DIR), and a DM + IR + SB203580 group. The control and streptozotocin-induced diabetic rats underwent a sham operation or left hilum occlusion for 90 min followed by reperfusion for 4 h. SB203580 was used to inhibit the p38 MAPK pathway. The pulmonary oxygenation index, inflammatory cytokines in the serum, lung edema, histopathology, oxidant stress, apoptosis, and phosphorylated/total-p38 MAPK protein levels were measured. Results The DIR group displayed greater concentrations of tumor necrosis factor-α, interleukin-6, and intercellular adhesion molecule-1 and increases in the wet weight-to-dry weight ratio, lung injury scores, malondialdehyde levels, and cellular apoptosis, and these effects were accompanied by lower pulmonary oxygenation compared with the CIR group ( P < 0.05). In the DIR group, the expression levels of p38 MAPK protein were significantly upregulated compared with those of the CIR group. Additionally, all of these alterations were attenuated in the DM + IR + SB203580 group compared with the DIR group. Conclusions Diabetes exacerbates LIRI by activating the p38 MAPK pathway. [ABSTRACT FROM AUTHOR]

Reciprocal signaling between stromal and tumor cells was believed to contribute to tumor cell proliferation and apoptosis in heterocellular systems. Herein we used the CO 2 -sensitive AIEgen as bioprobe to study the synergistic effect of stromal cells and tumor cells in a heterocellular system. The experimental results demonstrated that metabolic rates of living tumor cells in the co-culture system were still faster than that of stromal cell through the detection of CO 2 generation rate in living cell. All rates were, however, slower than that in homocellular system. It indicated that tumor cells would induce neighboring stromal cells to establish a common protection mechanism against foreign material invasion, which enhanced the cell activity and drug resistance. In addition, tumor cells in solid carcinoma exhibited delayed growth but less apoptosis in co-culture systems. Taken these results together, a bidirectional signaling pathway theory was proposed between tumor and stromal cells in co-culture system and could play a different and important role in anticancer drug molecules designs. [ABSTRACT FROM AUTHOR]