The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis.

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.

Candidate Effectors from Botryosphaeria dothidea Suppress Plant Immunity and Contribute to Virulence.

Fungal effectors play important roles in host-pathogen interactions. Botryosphaeria dothidea is an ascomycetous fungus that is responsible for the diseases of hundreds of woody plant species, including apple ring rot, which seriously affects apples worldwide. However, little is known about the effectors of B. dothidea. In this study, we analyzed the B. dothidea genome and predicted 320 candidate effector genes, 124 of which were successfully amplified and cloned. We investigated the effects of these genes on plant cell death in Nicotiana benthamiana while using a transient expression system. Twenty-four hours after initial inoculation with Agrobacterium tumefaciens cells carrying candidate effectors, the infiltrated leaves were challenged with A. tumefaciens cells carrying the BAX gene. In total, 116 candidate effectors completely inhibited, while one partially inhibited, the programmed cell death (PCD) of N. benthamiana induced by BAX, whereas seven candidate effectors had no effect. We then further tested seven candidate effectors able to suppress BAX-triggered PCD (BT-PCD) and found that they all completely inhibited PCD triggered by the elicitors INF1, MKK1, and NPK1. This result suggests that these effectors were activated in order to suppress pathogen-associated molecular pattern-triggered immunity. The signal peptides of these candidate effectors exhibited secretory activity in yeast (pSUC2 vector). Moreover, the respective deletion of Bdo_11198 and Bdo_12090 significantly reduced the virulence of B. dothidea. These results suggest that these effectors play important roles in the interaction of B. dothidea with its hosts.

Cross-talk of the related bioactivity mediators in serum after injection of soluble TNF-α receptor on silicosis model of rats.

This study investigates cross-talk of the related bioactivity mediators in silica-induced pulmonary inflammatory and fibrosis on rats, which contributes to the preventive and therapeutic effect of soluble TNF-α receptor. Wistar rats received saline or 50 mg of quartz by intratracheal instillation. Rats in drug-treated groups were given soluble tumor necrosis factor-α (TNF-α) receptor (500 µg) by hypodermic injection on days 1, 5 and 8 after operation. At 7 days or 14 days after instillation, rats were killed to observe the degree of injury and expression of the related bioactivity mediators including nuclear factor KB (NF-KB), nitric oxide, interleukin-1ß, interleukin-10, transforming growth factor beta 1 (TGF-ß1), TNF-α, interferon-Y (IFN-Y) and granulocyte macrophage colony-stimulating factor (GM-CSF). The area percentages of type I and III collagens in intervention group were lower than those in silica group. The expression of NF-κB, TGF-ß1, and COL I were lower in intervention group than in silica group(p < 0.05) and GM-CSF was significantly higher (p < 0.05) at 7 days after instillation, however, NF-κB, TGF-ß1, and COL I were identically lower in intervention group than in silica group, and TNF-α, IFN-γ, and GM-CSF were higher at 14 days after instillation. It may be concluded that soluble TNF-α receptor upregulating or downregulating the expression of the related bioactivity mediators results in decreasing lung injury induced by silica.

[Effect of combined application of deproteinised calf serum injection and acupuncture on cerebral ischemia in rats].

OBJECTIVE: To study the efficacy of combined application of deproteinised calf serum injection (DCSI) and acupuncture in treating cerebral ischemia (CI) in rats. METHODS: Ninety Wistar rats were randomly divided into control, CI model, Acupunct (acupuncture), DCSI, Acupunct + DCSI groups, with 18 cases in each group. CI model was duplicated by middle cerebral artery occlusion (MCAO). DCSI (80 mg/kg) was given via the rat's tail vein, once daily for 7 days. Acupuncture was applied to "Baihui" (GV 20), "Shuigou" (GV 26), "Neiguan" (PC 6), "Hegu" (LI 4), "Taichong" (LR 3) and "Zusanli" (ST 36), once daily for 7 days. The neurological deficit score (NDS), cerebral infarct volume (CIV), water and lactic acid (LA) contents in cerebral tissues were measured. RESULTS: In comparison with control group, NDS, CIV, cerebral water content and LA in model group increased significantly (P<0.05); while compared with model group, NDS, CIV, cerebral water content and LA in Acupunct, DCSI and Acupunct + DCSI groups decreased significantly (P<0.05). Comparison among DCSI group, Acupunct group and DCSI + Acupunct group showed that NDS, CIV, cerebral water and LA contents of Acupunct + DCSI group were significantly lower than those of the former two groups (P<0.05). No significant differences were found between DCSI and Acupunct groups in the above-mentioned 4 indexes (P>0.05). CONCLUSION: Combined application of DCSI and acupuncture has a definite effect in improving cerebral ischemia and is superior to that of simple acupuncture or DCSI alone.