Cell Cycle Arrest In Prostate Cancer Research Articles

The circHMGCS1-miR-205–5p-ErBB3 axis mediated the Sanggenon C-induced anti-proliferation effects on human prostate cancer

Prostate cancer (PCa) is associated with a high incidence and metastasis rate globally, resulting in an unsatisfactory prognosis and a huge economic burden due to the current deficient of therapeutic strategies. As the most abundant component of Cortex Mori, Sanggenon C (SC) is well known to possess bioactivities in tumors, but its mechanism is poorly understood. Consequently, we attempted to investigate whether SC could modulate circular RNA(s) levels and hence anti-PCa development. We found that SC dramatically promoted cell apoptosis and induced G0/G1 phase arrest in PCa cell lines via the circHMGCS1-miR-205–5p-ErBB3 axis. In brief, circHMGCS1 is highly expressed in PCa and is positively correlated with the degree of malignancy. Over-expression of circHMGCS1 is not only associated with the proliferation of PCa cells but also blocks SC-induced pro-apoptotic effects. As a verified sponge of circHMGCS1, miR-205–5p is down-regulated in PCa tumors, which negatively regulates PCa cell proliferation by modulating ErBB3 expression. After miR-205–5p mimics or inhibitors were used to transfect PCa cells, the effects of circHMGCS1 OE and SC on PCa cells were completely diminished. Similar to miR-205–5p inhibitors, siErBB3 could oppose SC-triggered pro-apoptotic effects on PCa cells. All these results were confirmed in vivo. Together, SC exerts its anti-tumor effects on PCa by inhibiting circHMGCS1 expression and results in the latter losing the ability to sponge miR-205–5p. Subsequently, unfettered miR-205–5p could mostly down-regulate ErBB3 expression by binding to the 5′UTR of ErBB3 mRNA, which eventually resulted in PCa cell cycle arrest and pro-apoptosis.

Polyphyllin I induces cell cycle arrest in prostate cancer cells via the upregulation of IL6 and P21 expression.

Polyphyllin I has been reported to possess anticancer properties in various cancer types, including prostate cancer. However, little is known about the potential of Polyphyllin I in induction of prostate cancer cell cycle arrest and its underlying mechanisms. The anti-proliferation activity of Polyphyllin I was tested using cell counting kit-8 assay. The cell cycle arrest effects of Polyphyllin I were confirmed by flow cytometry. Western blot was used to test the effect of Polyphyllin I on cell cycle-related protein expression. Reverse transcription-polymerase chain reaction was used to test the expression of genes regulating P21 expression. Polyphyllin I induced prostate cancer cell cycle arrest in G0/G1 phase in concentration-dependent manner. Polyphyllin I induced cell cycle arrest by upregulating the expression of P21. Further studies showed that the upregulation of p21 expression induced by Polyphyllin I via the upregulation of IL6 expression. Polyphyllin I could induce cell cycle arrest in G0/G1 phase in prostate cancer cells by upregulating the expression of P21 and IL6.

MicroRNA‑512‑3p is upregulated, and promotes proliferation and cell cycle progression, in prostate cancer cells.

Prostate cancer (PCa) is the most commonly diagnosed cancer in males worldwide. MicroRNAs (miRNAs/miRs) are small non‑coding RNAs that participate in the regulation of various biological processes by regulating post‑transcriptional gene expression. However, whether dysregulation of miRNA expression may be associated with the carcinogenesis of PCa remains to be elucidated. The present study identified differentially expressed miRNAs in PCa by analyzing two publicly available gene expression datasets, GSE14857 and GSE21036. The results demonstrated that miR‑512‑3p was significantly upregulated in PCa. Furthermore, the present study explored the molecular functions of miR‑512‑3p in PCa, and demonstrated that overexpression of miR‑512‑3p promoted PCa cell proliferation and reduced G1 phase cell cycle arrest in PCa. These results indicated that miR‑512‑3p may act as an oncogene in PCa. To the best of our knowledge, this is the first study revealed the molecular functions of miR‑512‑3p in PCa. To obtain valuable insights into the potential mechanisms of miR‑512‑3p, bioinformatics analyses were performed to identify the targets of miR‑512‑3p. Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology category analyses revealed that miR‑512‑3p may be associated with the mitogen‑activated protein kinase signaling pathway and numerous biological processes, including cell adhesion, cell proliferation, cell cycle and apoptosis. These results suggested that miR‑512‑3p may be considered a potential diagnostic and therapeutic target of PCa.

Androgen-induced miR-27A acted as a tumor suppressor by targeting MAP2K4 and mediated prostate cancer progression

Prostate cancer (PCa) is the most commonly diagnosed and secondly leading cause of cancer death among males. But the precise mechanism of prostate cancer progression, including microRNAs (miRNAs) functioning in it, is still needs further study. We found miR-27a to be down-regulated in prostate cancer, and we investigated the mechanism and role of miRNA-27a in prostate cancer. MiR-27a, a transcriptional target of AR, was an androgen-induced miRNA in LNCaP cells. In castration-resistant prostate cancer (CRPC) cells, we for the first time reported that miR-27a was downregulated by PI3K signaling. MiR-27a functioned as a tumor suppressor in prostate cancer. Over-expression of miR-27a decreased prostate cancer cell proliferation and migration, and induced prostate cancer cell cycle arrest and apoptosis. MAP2K4, miR-27a’s direct target gene, functioned as an oncogene in prostate cancer by reducing G1-S phase arrest and inhibiting cell apoptosis of prostate cancer cells. In conclusion, miR-27a functions as a tumor suppressor by suppressing MAP2K4 which acts as an oncogene in prostate cancer cell lines; we also provided a new mechanism of castration-resistant prostate cancer mediated by miR-27a that downregulation of miR-27a caused by aberrant AR signaling and PI3K/Akt signaling after androgen deprivation therapy (ADT) would promote the progression of castration-resistant prostate cancer.

Long Noncoding RNA MALAT-1 is a New Potential Therapeutic Target for Castration Resistant Prostate Cancer

To understand the role of MALAT-1 in prostate cancer we evaluated its expression in prostate cancer tissues and cell lines. We also studied the therapeutic effects of MALAT-1 silencing on castration resistant prostate cancer cells invitro and invivo. Quantitative reverse transcriptase-polymerase chain reaction was used to detect MALAT-1 expression in prostate cancer tissues and cell lines. siRNA against MALAT-1 was designed and the silencing effect was examined by quantitative reverse transcriptase-polymerase chain reaction. The biological effects of MALAT-1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays as well as cell migration by invitro scratch assay, cell invasion by Transwell® invasion assay and cell cycle by flow cytometry. We further investigated the effect of therapeutic siRNA targeting MALAT-1 on castration resistant prostate cancer invivo. MALAT-1 was up-regulated in human prostate cancer tissues and cell lines. Higher MALAT-1 expression correlated with high Gleason score, prostate specific antigen, tumor stage and castration resistant prostate cancer. MALAT-1 down-regulation by siRNA inhibited prostate cancer cell growth, invasion and migration, and induced castration resistant prostate cancer cell cycle arrest in the G0/G1 phases. Importantly, intratumor delivery of therapeutic siRNA targeting MALAT-1 elicited delayed tumor growth and reduced metastasis of prostate cancer xenografts in castrated male nude mice, followed by the concomitant prolongation of survival of tumor bearing mice. MALAT-1 may be needed to maintain prostate tumorigenicity and it is involved in prostate cancer progression. Thus, MALAT-1 may serve as a potential therapeutic target for castration resistant prostate cancer.

Mechanism of Growth Inhibition of Prostate Cancer Xenografts by Valproic Acid

Valproic Acid (VPA), a histone deacetylase inhibitor, has been demonstrated to cause a marked decrease in proliferation of prostate cancer (PCa) cells in vitro and a significant reduction in tumor volume in vivo. The goal of this study is to better understand the VPA-induced growth inhibition in vivo, by studying expression of various markers in PCa xenografts. Methods. For in vitro experiments, PCa cells were treated with 0, 0.6, and 1.2 mM VPA for 14 days. For in vivo models, experimental animals received 0.4% VPA in drinking water for 35 days. Tissue microarray was generated using cell pellets and excised xenografts. Results. VPA treatment causes cell cycle arrest in PCa cells in vivo, as determined by increase in p21 and p27 and decrease in cyclin D1 expression. Increased expression of cytokeratin18 was also seen in xenografts. LNCaP xenografts in treated animals had reduced androgen receptor (AR) expression. While decreased proliferation was found in vitro, increase in apoptosis was found to be the reason for decreased tumor growth in vivo. Also, an anti-angiogenic effect was observed after VPA treatment. Conclusion. VPA inhibits tumor growth by multiple mechanisms including cell cycle arrest, induction of differentiation, and inhibition of growth of tumor vasculature.