Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial-mesenchymal transition in clear-cell renal cell carcinoma.

RUNX3 is a transcription factor and tumor suppressor that is silenced or inactivated in diverse tumors. The effect of RUNX3 on the epithelial-mesenchymal transition in clear-cell renal cell carcinoma (CCRCC) remains unclear. We determined the expression of RUNX3 and E-cadherin in tumor tissues and adjacent normal tissues of 30 CCRCC patients; established cultured CCRCC cells with the overexpression of RUNX3; and examined the in vivo tumorigenic function of RUNX3 in a nude mouse xenograft model of CCRCC. RUNX3 and E-cadherin were downregulated in human CCRCC samples. Cell lines with RUNX3 overexpression had reduced cell proliferation, invasion, and migration, a prolonged cell cycle, increased apoptosis, and increased expression of E-cadherin. In the nude mouse xenograft model of CCRCC, tumors with the overexpression of RUNX3 had smaller volumes and weights and had increased expression of E-cadherin. In conclusion, RUNX3 overexpression increased the level of E-cadherin and inhibited the proliferation, invasion, and migration of CCRCC in vitro and in vivo. RUNX3 has potential use as a biomarker for prognostic monitoring of CCRCC and as a therapeutic target for the treatment of this cancer.

The prognostic value of C-reactive protein/albumin ratio in nasopharyngeal carcinoma: a meta-analysis.

The C-reactive protein/albumin ratio (CRP/Alb ratio) has been reported to have promising prognostic value in several cancers. The current meta-analysis was conducted to better define the prognostic value of CRP/Alb ratio in patients with nasopharyngeal carcinoma (NPC). The Web of Science, Embase, Cochrane Library databases, and PubMed were searched up to 25 February 2018 for the information on CRP/Alb ratio and outcomes of NPC. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were used to evaluate the association between CRP/Alb ratio and survival outcomes in NPC. A total of five studies with 5533 patients with NPC were included. Pooled results showed that high CRP/Alb ratio was associated with poor overall survival (OS) (HR = 1.51, 95% CI: 1.30-1.75, P<0.001) and poor distant metastasis-free survival (DMFS) (HR = 1.23, 95% CI: 1.07-1.43, P=0.005). Subgroup analyses showed that patients with higher CRP/Alb ratio have worse OS in NPC. In conclusion, elevated CRP/Alb ratio was associated with worse prognosis in patients with NPC.

Key site residues of pheromone-binding protein 1 involved in interacting with sex pheromone components of Helicoverpa armigera.

Pheromone binding proteins (PBPs) are widely distributed in insect antennae, and play important roles in the perception of sex pheromones. However, the detail mechanism of interaction between PBPs and odorants remains in a black box. Here, a predicted 3D structure of PBP1 of the serious agricultural pest, Helicoverpa armigera (HarmPBP1) was constructed, and the key residues that contribute to binding with the major sex pheromone components of this pest, (Z)-11- hexadecenal (Z11-16:Ald) and (Z)-9- hexadecenal (Z9-16:Ald), were predicted by molecular docking. The results of molecular simulation suggest that hydrophobic interactions are the main linkage between HarmPBP1 and the two aldehydes, and four residues in the binding pocket (Phe12, Phe36, Trp37, and Phe119) may participate in binding with these two ligands. Then site-directed mutagenesis and fluorescence binding assays were performed, and significant decrease of the binding ability to both Z11-16:Ald and Z9-16:Ald was observed in three mutants of HarmPBP1 (F12A, W37A, and F119A). These results revealed that Phe12, Trp37, and Phe119 are the key residues of HarmPBP1 in binding with the Z11-16:Ald and Z9-16:Ald. This study provides new insights into the interactions between pheromone and PBP, and may serve as a foundation for better understanding of the pheromone recognition in moths.

RNAi-Induced Electrophysiological and Behavioral Changes Reveal two Pheromone Binding Proteins of Helicoverpa armigera Involved in the Perception of the Main Sex Pheromone Component Z11-16:Ald.

Pheromone binding proteins (PBPs) are thought to play key roles in insect sex pheromone recognition; however, there is little in vivo evidence to support this viewpoint in comparison to abundant biochemical data in vitro. In the present study, two noctuid PBP genes HarmPBP1 and HarmPBP2 of the serious agricultural pest, Helicoverpa armigera were selected to be knocked down by RNA interference, and then the changes in electrophysiological and behavioral responses of male mutants to their major sex pheromone component (Z)-11-hexadecenal (Z11-16:Ald) were recorded. There were no significant electrophysiological or behavioral changes of tested male moths in response to Z11-16:Ald when either single PBP gene was knocked down. However, decreased sensitivity of male moths in response to Z11-16:Ald was observed when both HarmPBP1 and HarmPBP2 genes were silenced. These results reveal that both HarmPBP1 and HarmPBP2 are required for the recognition of the main sex pheromone component Z11-16:Ald in H. armigera. Furthermore, these findings may help clarify physiological roles of moth PBPs in the sex pheromone recognition pathway, which in turn could facilitate pest control by exploring sex pheromone blocking agents.

Molecular characterization and differential expression of olfactory genes in the antennae of the black cutworm moth Agrotis ipsilon.

Insects use their sensitive and selective olfactory system to detect outside chemical odorants, such as female sex pheromones and host plant volatiles. Several groups of olfactory proteins participate in the odorant detection process, including odorant binding proteins (OBPs), chemosensory proteins (CSPs), odorant receptors (ORs), ionotropic receptors (IRs) and sensory neuron membrane proteins (SNMPs). The identification and functional characterization of these olfactory proteins will enhance our knowledge of the molecular basis of insect chemoreception. In this study, we report the identification and differential expression profiles of these olfactory genes in the black cutworm moth Agrotis ipsilon. In total, 33 OBPs, 12 CSPs, 42 ORs, 24 IRs, 2 SNMPs and 1 gustatory receptor (GR) were annotated from the A. ipsilon antennal transcriptomes, and further RT-PCR and RT-qPCR revealed that 22 OBPs, 3 CSPs, 35 ORs, 14 IRs and the 2 SNMPs are uniquely or primarily expressed in the male and female antennae. Furthermore, one OBP (AipsOBP6) and one CSP (AipsCSP2) were exclusively expressed in the female sex pheromone gland. These antennae-enriched OBPs, CSPs, ORs, IRs and SNMPs were suggested to be responsible for pheromone and general odorant detection and thus could be meaningful target genes for us to study their biological functions in vivo and in vitro.

Molecular identification and differential expression of sensory neuron membrane proteins in the antennae of the black cutworm moth Agrotis ipsilon.

The insect sensory neuron membrane proteins (SNMPs) SNMP1 and SNMP2 are transmembrane domain-containing proteins and are homologs of the vertebrate CD36 transmembrane proteins. It has been suggested that SNMPs play a significant role in insect chemoreception. Previous studies have demonstrated that SNMP1 is expressed in the pheromone-sensitive olfactory receptor neurons (ORNs), whereas SNMP2 is expressed in the supporting cells. In this study, we identified two full-length SNMP transcripts, AipsSNMP1 and AipsSNMP2, in the black cutworm moth Agrotis ipsilon (Hufnagel). The qRT-PCR results indicated that the AipsSNMP1 and AipsSNMP2 transcripts were expressed significantly higher in the antennae than in other tissues of both sexes. The expression of AipsSNMP1 and AipsSNMP2 in the antennae from different development stages of both sexes was investigated and was shown to begin to express in the pupae stage from 3days before emergence and then increased dramatically at the day of the emergence, and the high expression levels were maintained during the following 4days after the emergence in both sexes. The mating status had no effect on the expression levels of the AipsSNMP1 and AipsSNMP2 transcripts. Consistent with previous in situ hybridization studies in other Lepidoptera insects, our immunolocalization results at protein level demonstrated that both AipsSNMP1 and AipsSNMP2 were expressed in pheromone-sensitive sensilla trichodea but with a completely different expression profile. AipsSNMP1 is more uniformed and highly expressed along the membrane of the ORN dendrites, whereas AipsSNMP2 is widely distributed at the bottom of the sensilla trichodea and highly localized in the sensillum lymph. Our studies provide further detailed evidence for the involvement and general functional role of insect SNMPs in the detection of sex pheromones and general odorant molecules.