Cholinergic α5 nicotinic receptor is involved in the proliferation and invasion of human prostate cancer cells

Abstract

Nicotinic acetylcholine receptor (nAChR) subunit α5 (α5-nAChR) is involved in tumor cell proliferation, inhibition of apoptosis, progression of metastasis, and induction of angiogenesis in certain solid tumors. However, the role of α5-nAChR in prostate cancer cell growth and metastasis is unclear. In the present study, the role of α5-nAChR in cell proliferation, migration, invasion and apoptosis was investigated by silencing the expression levels of α5-nAChR in the prostate cancer cell lines DU145 and PC3. A siRNA oligonucleotide targeting α5-nAChR was designed. The cell proliferation of DU145 and PC3 cell lines was analyzed by the Cell Counting Kit-8 (CCK-8) assay. Cell migratory and invasive activities were determined using wound healing and Transwell assays, respectively. Western blot analysis was used to quantify α5-nAChR, p-AKT and p-ERK1/2 levels in DU145 and PC3 cells. Knockdown of α5-nAChR was associated with decreased cell proliferation, migration, invasion and increased apoptosis. In addition, decreased phosphorylation levels of AKT and ERK1/2 were revealed following α5-nAChR knockdown in DU145 and PC3 cells compared with those observed in the scramble control samples. The expression levels of the apoptosis-related proteins were altered following silencing of α5-nAChR. In summary, the data indicated that α5-nAChR was involved in the proliferation and invasion of human prostate cancer cells.

SIRT5 Directly Inhibits the PI3K/AKT Pathway in Prostate Cancer Cell Lines

“…Interestingly, it was demonstrated that the SIRT5/PI3K axis mediated extremely high levels of IL-1β mRNA and protein in SIRT5 KO cells. Positive transcriptional regulators of this pathway, such as p50/65, were also induced in SIRT5 KO cells (40). IL-1β expression is positively correlated with bone metastasis in breast cancer, wherein IL-1β up-regulates VEGF and its corresponding receptor on endothelial cells to facilitate EC migration (41).…”

Advances in Targeting Cancer-Associated Genes by Designed siRNA in Prostate Cancer

“…To assess the precise role of α5-nAChR in PCa, siRNA was used to silence α5-nAChR in PCa cell lines, DU145 and PC3. Results demonstrated that knockdown of α5-nAChR causes reduced levels of phospho-AKT and phospho-ERK1/2, followed by a significant decrease in cell migration and invasion and an induction of apoptosis, indicating the impact of α5-nAChR on the proliferation and invasion of human PCa cells and the importance of its silencing in PCa treatment [43]. Finally, six transmembrane epithelial antigens of the prostate 1 (STEAP1) was shown to be overexpressed in various types of tumors, particularly in PCa, and knockdown of STEAP1 in LNCaP cells by siRNA decreases cell viability and proliferation, whilst promoting apoptosis [44].…”

“…Macrophage-capping protein (CAPG) Reduces proliferatory, migratory, and invasive capacities of DU145 cells [54] Nicotinic acetylcholine receptor (nAChR) Decreases cell migratory and invasive activities, and induces apoptosis of DU145 and PC-3 cells. [43] Six transmembrane epithelial antigen of the prostate 1 (STEAP1)…”

Nicotinic Acetylcholine Receptors as Potential Tumor Biomarkers in Genitourinary Cancers: a Review Study

“…The subunit α5 of nAChRs as an important member of the nAChR family is involved in the proliferation and invasion of human PCa cells. 12 Magnon et al reported that autonomic nerve development contributes to PCa initiation and dissemination. 67 In this study, through the use of animal models of PCa, the authors demonstrated the role of the parasympathetic nervous system (PNS) in PCa development and progression.…”

“…Nicotinic receptors express by many different types of genitourinary cells such as kidney, 10 bladder, 11 prostate, 12 testicular, 13 penile, 14 cervical, 15 ovarian, 16 uterine, 17 as well in their cancerous cells. Among the different subunits of nAChR, previous reports indicated that the nAChRs are associated with different genitourinary cancersrelated properties including CSC renewal, proliferation, metastasis, angiogenesis, and suppression of apoptosis (Figure 2).…”