Mechanism of LncRNA ROR promoting prostate cancer by regulating Akt.

We detected some serious inaccuracies and mistakes. Therefore, the article "Mechanism of LncRNA ROR promoting prostate cancer by regulating Akt, by X.-Q. Zhai, F.-M. Meng, S.-F. Hu, P. Sun, W. Xu, published in Eur Rev Med Pharmacol Sci 2019; 23 (5): 1969-1977-DOI: 10.26355/eurrev_201903_17235-PMID: 30915739" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17235.

Mechanism of LncRNA ROR promoting prostate cancer by regulating Akt.

OBJECTIVE: To investigate the expression of long-chain non-coding RNA ROR in prostate cancer (PCa), and to further study its possible underlying mechanisms in prostate cancer. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the level of lncRNA ROR in 42 pairs of PCa tissues and adjacent normal tissues, and the correlation between ROR level and PCa pathological parameters was also evaluated. Besides, ROR expression in PCa cells was further verified by qRT-PCR, and ROR knockdown model was constructed using lentivirus in PCa cell lines including PC-3 and Lncap. Cell counting kit-8 (CCK-8), transwell invasion and cell scratch assay were used to analyze the effect of ROR on the biological function of PCa cells and explore its underlying mechanism. RESULTS: QRT-PCR results demonstrated that ROR levels in PCa tissues were notably higher than that in normal ones, and the difference was statistically significant. Compared with patients with lowly-expressed ROR, patients with high ROR level had relatively more advanced tumor stage, higher incidence of lymph node or distant metastasis. Similarly, compared with negative control group, the cell proliferation, invasion and metastasis ability of the ROR knockdown group was significantly decreased. In addition, qRT-PCR results indicated that the expression of Akt, the key protein in the Akt signaling pathway, was significantly reduced in si-ROR cell lines. Furthermore, rescue experiment revealed that there was a mutual regulation between ROR and Akt. CONCLUSIONS: LncRNA ROR expression is strikingly increased in PCa tissues or cells, and is considerably associated with PCa stage, lymph node and distant metastasis. Additionally, LncRNA ROR may promote PCa cell proliferation, invasion and migration by regulating Akt.

Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants.

Mutations in the kinase domain of epidermal growth factor receptor (EGFR) are associated with clinical responsiveness to gefitinib in patients with non-small-cell lung cancers (NSCLC). Recently, we have identified many novel EGFR mutations in NSCLC tissues. In this study, we found that gefitinib could suppress the tyrosine phosphorylation of most EGFR mutants better than the wild-type receptor. However, gefitinib had quite variable growth-suppressive effects on different EGFR mutant-expressing cells. All tested EGFR mutants have high basal phosphorylation at multiple tyrosine residues. Upon EGF stimulation, the mutated EGFRs did not have apparently stronger phosphorylation at tyrosines 845, 992, 1,068, and 1,173 than the wild-type receptor. However, stronger phosphorylation at tyrosine 1,045 was observed in the S768I, L861Q, E709G, and G719S mutants. The E746-A750 deletion mutant was less responsive to EGF than the wild-type and other mutant receptors. The S768I, L861Q, E709G, and G719S mutants were refractory to EGF-induced ubiquitination and had more sustained tyrosine phosphorylation. E709G and G719S also lacked EGF-induced receptor downregulation. Our results indicate that, in addition to sensitivity to gefitinib, EGFR mutations also caused various changes in EGFR's regulatory mechanisms, which may contribute to the constitutive activation of EGFR mutants and oncogenesis in NSCLC.

Transient scrotal hyperthermia affects human sperm DNA integrity, sperm apoptosis, and sperm protein expression.

This prospective randomized clinical study is aimed to evidence the reproductive impairment of frequent scrotal heat exposure. A total of 20 normozoospermic subjects were randomly divided into two groups to undergo testicular warming in a 43 °C water bath 10 times, for 30 min each time; the subjects in group 1 underwent testicular warming for 10 consecutive days and those in group 2 once every 3 days. Sperm chromatin structure assay (SCSA), sperm mitochondrial membrane potential (MMP), apoptosis, and seminal plasma-soluble Fas (sFas) were analyzed before treatment and every 2 weeks after, for a total of 10 times. In group 1, some critical proteins involved in heat stress, hypoxia, structure, and function of sperm mitochondria and flagella were evaluated before hyperthermia and 2, 6, 10, and 16 weeks after hyperthermia. Both groups showed a reversible increase in the proportion of spermatozoa with a disrupted MMP (both p < 0.05 when the minimums were compared with baseline levels, the same below), sperm apoptosis (both p < 0.01) and high DNA stainability (both p < 0.05). The sFas concentration in both groups showed no obvious changes except one: the value at week 2 was significantly increased over baseline in group 1 (p = 0.036). The level of Bcl-2 decreased significantly at weeks 6 and 10 (p = 0.017 and 0.05, respectively) and recovered to baseline at week 16. Proteins involved in heat stress and mitochondria functions were up-regulated, whereas in flagella structure and function was down-regulated (all p < 0.05). This study demonstrated that transient and frequent scrotal hyperthermia severely and reversibly damaged spermatogenesis, consecutive heat exposure had more serious effects than intermittent exposure, whereas intermittent exposure led to a later recovery of sperm damage.

Beta-arrestin1 and 2 differently modulate metabotropic glutamate receptor 7 signaling in rat developmental sevoflurane-induced neuronal apoptosis.

Beta-arrestins (ß-arrs) are initially known as negative regulators of G protein-coupled receptors (GPCRs). Recently, there is increasing evidence suggesting that ß-arrs also serve as scaffolds and adapters that mediate distinct intracellular signal transduction initiated by GPCR activation. In the previous study, we have shown that metabotropic glutamate receptor 7 (mGluR7) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling may be involved in the developmental sevoflurane neurotoxicity. In the present study, we showed that activation of mGluR7 with a group III mGluRs orthosteric agonist LAP4 or an atypical mGluR7 allosteric agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) significantly attenuated sevoflurane-induced neuronal apoptosis. Interestingly, this neuroprotective role of LAP4 could be partially reduced by ß-arr1 small interfering RNA (siRNA) or ß-arr2 siRNA transfection. In contrast, ß-arr2 siRNA transfection alone abolished the effects of AMN082 on sevoflurane neurotoxicity. In addition, administration of LAP4 or AMN082 significantly enhanced Phospho-ERK1/2 in sevoflurane neurotoxicity, which could be abrogated by ß-arr2 siRNA transfection, but not by ß-arr1 siRNA transfection. Increased ß-arr2-dependent Phospho-ERK1/2 signaling alleviated sevoflurane neurotoxicity by inhibiting bad phosphorylation. We also found that the neuroprotective role of AMN082 was completely reversed by ERK1/2 inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126). Alternatively, treatment with U0126 partially suppressed the neuroprotective of LAP4, suggesting that other mechanisms may be implicated in this process. Further investigation indicated that, in the scenario of sevoflurane neurotoxicity, application of LAP4 (but not AMN082) increased the interaction of ß-arrs with transcriptional factors CREB binding protein (CBP) and p300. LAP4 also enhanced the ß-arr1-dependent H3 and H4 acetylation in sevoflurane neurotoxicity. For the behavior study, treatment with LAP4 or AMN082 significantly improved the emotional and spatial learning and memory disorders induced by postnatal sevoflurane exposure. These results suggested that ß-arr1 and 2 may differently modulate mGluR7 signaling in developmental sevoflurane neurotoxicity. This study also reveals a ß-arr-biased agonism at GPCRs (e.g. mGluR7).

Lycorine alkaloids from Hymenocallis littoralis.

From Hymenocallis littoralis, one new alkaloid, named littoraline, together with 13 known lycorine alkaloids and one lignan, were isolated. The structure and NMR assignments of this new alkaloid were determined by 1D and 2D NMR techniques. Littoraline showed inhibitory activity of HIV reverse transcriptase, and lycorine and haemanthamine showed potent in vitro cytotoxicity.

Phenolic aporphine-benzylisoquinoline alkaloids from Thalictrum faberi.

From the roots of Thalictrum faberi, six new phenolic aporphine-benzylisoquinoline alkaloids, 3-hydroxy-6'-desmethyl-9-O-methylthalifaboramine (1), 3-hydroxythalifaboramine (2), 6'-desmethylthalifaboramine (3); 3,5'-dihydroxythalifaboramine (4), 5'-hydroxythalifaboramine (5) and 3-hydroxy-6'-desmethylthalifaboramine (6) were isolated. Their structures were established through the use of one- and two-dimensional NMR techniques. All of the tested alkaloids showed potent cytotoxic and antimalarial activities.

[Detection of serum immunoglobulins in pulmonary acariasis patients].

The IgG, IgA, IgM levels in sera of 51 patients suffered from pulmonary ascariasis and the serum IgE level in 16 of them were determined using single immunodiffusion technique or biotin-avidin enzyme immunosorbent assay (ABC-ELISA). The results showed that the IgM level of the patients was approaching to that of the normals while IgG (169.77 +/- 46.91 U/ml), IgA (308.39 +/- 91.83 U/ml) and IgE (458.90 +/- 273.64 U/ml) levels of the patients increased significantly. This suggests that some components of mites may have stimulated the humoral immunoreactions of the host.

[Clinical manifestation and treatment of pulmonary acariasis].

A survey on pulmonary acariasis was carried out in the grain store and in the Chinese medicinal herb plant. Of 363 persons examined, 92(25.3%) were mites-positive in their sputum. 65 of them had symptoms and signs attributed to pulmonary acariasis, the incidence being 17.9%. The main clinical manifestations were productive cough, hemoptysis, chest pain, dyspnea asthma and marked eosinophilia. Roentgenogram of these cases revealed widening hilum shadow, increased and disordered lung markings, multiple cloudy shadow and nodular opacities ranging from 1-5mm in diameter scattered throughout the lower field of lungs. All the patients were treated with three courses of metronidazole. In each course a daily dose of 0.6g (0.2g tid) or 0.8g (0.4g bid) was given orally for seven days with an interval of 7-10 days between two courses. After three courses, the clinical manifestations and radiographic findings were much improved in most cases, eosinophilia dropped to normal limit, mites disappeared from sputum in 94.4% of patients. All these showed that metronidazole is rather effective in treating pulmonary acariasis.

NF-Y-mediated trans-activation of the human thymidine kinase promoter is closely linked to activation of cyclin-dependent kinase.

Transcriptional activation is important for the elevated expression of human thymidine kinase (hTK) in tumor cells. Here, we used TK(-133/+33)-luciferase reporter gene construct and bandshift assay to study the cis-elements involved in transcriptional activation of the hTK promoter. We found that two CCAAT boxes at -71/-67 and -40/-36 and Sp1 binding site located at -118/-113 were critical for maximal expression of the hTK promoter activity. As Sp1-mediated activation of the hTK promoter was not detectable for the promoter construct with double mutations at two CCAAT boxes, we proposed that NF-Y binding to the hTK promoter sequence is a requisite step for the functional interaction with Sp1. Here, we further showed that the hTK promoter activity was reduced in HeLa cells transfected with p16 or p21, both of which are inhibitors of cyclin-dependent kinases (CDKs). Inhibition of the hTK promoter activity by p16 could be abrogated by overexpression of cyclin A, indicating that the cyclin A activating event is more directly involved in transcriptional activation of the hTK promoter. We thus proposed that NF-Y-mediated activation of the hTK promoter is closely linked to the activation of CDK2/cyclin A pathway.

Characterization of the env gene in avian oncoviruses by heteroduplex mapping.

The genome of ring-necked pheasant virus, an avian oncovirus, is largely homologous to the genomes of chicken oncoviruses except for a specific nonhomology in env, the gene coding for the surface glycoprotein of the virion (J. Tal, D. J. Fujita, S. Kawai, H. E. Varmus, and J. M. Bishop, J. Virol. 21:497--505, 1977). We have used this nonhomology between ring-necked pheasant virus and chicken oncoviruses in electron microscopic studies of heteroduplex molecules. The env-specific region of nonhomology is 1.5 to 1.7 kilobases in length. Its 3' boundary is located 0.6 to 0.7 kilobases from the 3' end of the genome in transformation-defective viruses and 2.5 kilobases from the 3' end in nondefective avian sarcoma viruses. Comparison of several strains of avian oncoviruses shows that the 3' half of this env region is conserved, while the 5' half is more diverged. A small area at the very 3' end of env also shows divergence between different avian oncoviruses. We found no evidence for the presence of a previously unrecognized gene between env and src. An electrophoretic comparison of the glycoproteins from various avian oncoviruses shows that those of ring-necked pheasant virus and Chinese quail virus differ in molecular weight from the glycoproteins of the chicken oncoviruses.

Thalifaberidine, a cytotoxic aporphine-benzylisoquinoline alkaloid from Thalictrum faberi.

From Thalictrum faberi, thalifaberidine [1], a new aporphine-benzylisoquinoline alkaloid, together with four known alkaloids, thalifaramine [2], thalifaricine [3], thalifarazine [4], and thalifaronine [5], were isolated. Thalifaberidine [1] was identified as 6',8-desmethylthalifaberine, and its 1H- and 13C-nmr data were completely assigned through the use of one- and two-dimensional nmr techniques. Thalifaberidine [1], thalifaberine [6], and thalifasine [7] showed cytotoxic activity against several human cancer cell lines, as well as antimalarial activity.