Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway

Abstract

Background/Aims: The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line. Methods: The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression. Results: At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile. Conclusions: The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.

miR-296-5p suppresses EMT of hepatocellular carcinoma via attenuating NRG1/ERBB2/ERBB3 signaling

“…In the current study, miR-296-5p showed a positive correlation with E-cadherin level, and both in vitro and in vivo experiments also demonstrated that miR-296-5p could reverse the EMT phenotype and metastatic capability in HCC cells. NRG1, a member of NRG family, is known as a key growth factor for the development of the normal nervous system and the occurrence of schizophrenia, which is also involved in cancer progression [ 38 , 39 ]. The relationship between miR-296-5p and NRG1 in HCC was further clarified here.…”

Hypoxia regulates human mast cell adhesion to fibronectin via the PI3K/AKT signaling pathway

“…HPRT1, HMBS, RPL13A primer sequences were taken from the work of Vandesompele et al [48]. Integrin and PI3K primer sequences were published elsewhere: ITGA1, ITGA5, ITGA7, ITGA8, ITGA9, ITGA11, ITGAV, ITGB1, ITGB3, ITGB4 [49], ITGA2 [50], ITGA3 [51], ITGA4 [52], ITGAE [53], ITGB2 [54], ITGB5 [55], PIK3CA [56], PIK3CB [57], PIK3CD, PIK3R3 [58], PIK3R1 [59], PIK3R4 [60], PIK3C2B [61]. Other sequences were design using Primer3 software [62] or PrimerBlast [63].…”

PIK3Cδ expression by fibroblasts promotes triple-negative breast cancer progression

“…opposed to AURKA, which was ubiquitously expressed ( Figure 2C, Supplemental Figure 1C, and Supplemental Figure 4D, upper panel). Quantitative reverse transcriptase PCR (qRT-PCR) analysis of PIK3Cδ revealed a similar trend for most of the cell lines tested (Supplemental Figure 4A), though it is well known that protein and mRNA abundances do not always correlate (25,26). Moreover, RNA sequencing (RNA-Seq) in different organs obtained from the Human Protein Atlas (27) revealed that, apart from myeloid and lymphoid cells, fibroblast cell lines express moderate/high PIK3Cδ mRNA levels, in contrast to BC cell lines, which have low/ negligible mRNA transcripts (Supplemental Figure 4B).…”