The expression level of lysophosphatidylcholine acyltransferase 1 (LPCAT1) correlates to the progression of prostate cancer

Introduction: Prostate cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide. In the present study, the expression level of glycine N-methyl transferase gene (GNMT) was investigated in prostate cancer tissue. The GNMT enzyme is encoded by the GNMT gene. Increased GNMT gene expression increases the conversion of glycine to sarcosine and results in the elevated levels of sarcosine in blood and urine. Methods: The expression level of GNMT gene in tissue samples of patients with prostate cancer was compared with those with benign prostatic hyperplasia using Real-Time PCR technique. Results: The GNMT gene expression level increased significantly in prostate cancer patients compared with those with benign prostatic hyperplasia (p-value <0.001). In addition, the expression level of GNMT gene was stage-dependent and significant increases were observed in all stages of prostate cancer compared with those with benign prostatic hyperplasia (p-value <0.001). Conclusion: The concentration of sarcosine is controlled by GNMT and it seems that increasing the expression level of GNMT gene increases the level of sarcosine concentration. Thus, it appears that increased levels of GNMT expression occur in the early stages of prostate cancer. Therefore, periodic measurement of GNMT expression levels can detect prostate cancer before it forms a cancer cell and invades other tissues.

Download Full-text

Up-Regulation of LINC00665 Facilitates the Malignant Progression of Prostate Cancer by Epigenetically Silencing KLF2 Through EZH2 and LSD1

Frontiers in Oncology ◽

10.3389/fonc.2021.639060 ◽

2021 ◽

Vol 11 ◽

Author(s):

Peng Xue ◽

Miao Yan ◽

Kunpeng Wang ◽

Jinbao Gu ◽

Bing Zhong ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Malignant Progression ◽

Expression Level ◽

Regulation Mechanism ◽

Knock Down ◽

Qrt Pcr ◽

Mouse Xenograft Model ◽

Du145 Cells

This study aimed to explore the function of LINC00665 on the proliferation and metastasis of prostate cancer (PCa), and the potential regulatory mechanisms were also investigated. The expression level of LINC00665 in 50 pairs of PCa tissues and adjacent ones was studied by qRT-PCR, and the associations between LINC00665 and clinicopathological characteristics of PCa patients were analyzed. Control group (sh-NC) and LINC00665 knock-down group (sh-LINC00665) were set in 22RV1 and DU145 cells, respectively. The biological functions of LINC00665 in PCa cell lines were assessed by CCK-8, EdU, Transwell assays, and the nude mouse xenograft model was used to evaluate the tumorigenicity in vivo. In addition, qRT-PCR, Western Blot, RIP and ChIP assays were also used to determine the regulation mechanism of LINC00665 in PCa cell lines. In this study, our results showed that LINC00665 expression level in PCa cancer tissues was significantly up-regulated, compared with that in adjacent ones. Besides, similar results were found in PCa cell lines. Knock-down of LINC00665 significantly attenuated the proliferation and migration ability in 22RV1 and DU145 cells, compared to sh-NC. Mechanically, LINC00665 could interact with EZH2 and LSD1, recruiting them to KLF2 promoter region to inhibit its transcription. Moreover, the tumor-suppressive effects mediated by sh-LINC00665 were significantly reversed through the down-regulation of KLF2. Also, the suppression of LINC00665 impaired tumor growth of PCa in vivo. In summary, LINC00665 exerted the oncogenic functions in PCa cell lines by epigenetically silencing KLF2 expression by binding to EZH2 and LSD1, illuminating a novel mechanism of LINC00665 in the malignant progression of PCa and furnishing a prospective therapeutic biomarker to combat PCa.

Download Full-text

IMP3 accelerates the progression of prostate cancer through inhibiting PTEN expression in a SMURF1-dependent way

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01657-0 ◽

2020 ◽

Vol 39 (1) ◽

Author(s):

Xiang Zhang ◽

Dawei Wang ◽

Boke Liu ◽

Xingwei Jin ◽

Xianjin Wang ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Viability ◽

Signaling Pathway ◽

Cell Lines ◽

Western Blotting ◽

Cell Apoptosis ◽

Expression Level ◽

Mtor Signaling Pathway ◽

Expression Levels ◽

Cancer Tissues

Abstract Background Insulin-like growth factor 2 (IGF2) messenger RNA binding protein 3 (IMP3) has been testified to be overexpressed in prostate cancer and strongly related to patients’ poor prognosis. However, the functions of IMP3 and the underlying mechanisms in prostate cancer still remain unknown. Therefore, the current study was carried out to reveal the role and molecular mechanism of IMP3 in prostate cancer progression. Methods The expression levels of IMP3 in prostate cancer tissues and cells were detected by immunohistochemistry (IHC), western blotting and RT-PCR. CCK-8, clone formation, flow cytometry and in vivo tumor formation assays were used to determine cell growth, clone formation apoptosis and tumorigenesis, respectively. The effect of IMP3 on the expression levels of the key proteins in PI3K/AKT/mTOR signaling pathway, including PIP2, PIP3, p-AKT, AKT, p-mTOR, mTOR, PTEN and BAD activation of was determined by western blotting. IP (Immunoprecipitation) assay was used to evaluate the effects of IMP3 and SMURF1 (SMAD specific E3 ubiquitin protein ligase 1) on the ubiquitination of PTEN protein. Results IMP3 expression level was significantly increased in prostate cancer tissues and cell lines (LNCap, PC3 and DU145) as compared with the paracancerous normal tissues and cells (RWPE-1), respectively. High expression of IMP3 apparently promoted cell viability, tumorigenesis and inhibited cell apoptosis in prostate cancer LNCap, DU145 and PC3 cell lines. In mechanism, IMP3 upregulation significantly increased the phosphorylation levels of AKT and mTOR, and elevated PIP3 expression level, while induced significant reductions in the expression levels of BAD, PTEN and PIP2. And, IMP3 overexpression increased SMURF1 expression, which facilitated PTEN ubiquitination. In addition, SMURF1 overexpression enhanced prostate cancer cell viability and inhibited cell apoptosis. Silence of SMURF1 rescued the enhancements in cell proliferation and tumorigenesis and the inhibition in cell apoptosis rates induced by IMP3 in prostate cancer DU145 and LNCap cells. Conclusion This study reveals that IMP3 is overdressed in prostate cancer, which accelerates the progression of prostate cancer through activating PI3K/AKT/mTOR signaling pathway via increasing SMURF1-mediated PTEN ubiquitination.

Download Full-text

Integrative Analysis of microRNA Expression Level Profile Identifies microRNAs associated with Prostate Cancer

Gene Reports ◽

10.1016/j.genrep.2021.101376 ◽

2021 ◽

pp. 101376

Author(s):

Opeyemi Soremekun ◽

Chisom Ezenwa ◽

Oluwatomiwa Paimo ◽

Chijioke Madu ◽

Olabode Omotoso ◽

...

Keyword(s):

Prostate Cancer ◽

Integrative Analysis ◽

Microrna Expression ◽

Expression Level ◽

Level Profile

Download Full-text

Altered staining patterns and expression level of Engrailed-2 in Benign prostatic hyperplasia and Prostate Cancer predict Prostatic disease progression

10.21203/rs.2.14625/v3 ◽

2020 ◽

Author(s):

Qi Li ◽

Yibo Shi ◽

Rigai Sa ◽

Jun Hao ◽

Jinhao Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Monoclonal Antibody ◽

Benign Prostatic Hyperplasia ◽

Disease Progression ◽

Cell Lines ◽

Immunohistochemical Staining ◽

Prostatic Hyperplasia ◽

Expression Level ◽

Clinical Staging ◽

Rt Pcr

Abstract Background: Prostate cancer (PC) , a common malignant tumor, is the second-leading cause of cancer death among American men. Its successful treatment greatly relies on the early diagnose. Engrailed-2 (EN2) has been confirmed being existed with a high level in the urine of PC patients. In this study, to explore the application of EN2 in PC, we detected the immunohistochemical staining difference and EN2 expression level between benign prostatic hyperplasia (BPH) and PC. Methods: We developed a monoclonal antibody against the helix 3 in EN2 and confirmed its specificity with Western blotting (WB) and immunofluorescence detecting the subcellular localization of endogenous and exogenous EN2 in three PC cell lines (LNCap, PC3, and DU145). We conducted immunohistochemical staining using this homemade antibody, and RT-PCR to detect the expression of EN2 in 25 PC and 25 BPH cases , and analyzed the correlation of EN2 expression and PC clinical staging. Results: The results of WB and immunofluorescence showed our homemade EN2 monoclonal antibody could specifically bind endogenous and exogenous EN2 protein in three different PC cell lines. Endogenous EN2 was generally expressed in the cytoplasm and exogenous EN2 mostly existed in the nucleus of these cell lines. Immunohistochemical staining in PC had extremely stronger signals than that in BPH, suggesting a higher EN2 expression level in PC, which was confirmed by RT-PCR. Interestingly, the stained areas in BPH tissues were mainly in nucleus and cytoplasm, while in PC tissues were mainly on cytomembrane. Moreover, the expression level of EN2 was positively correlated with the PC clinical staging. Conclusion: Using our homemade EN2 antibody, we have found different staining patterns and expression level of EN2 in BPH and PC，which may be helpful to predict prostatic disease progression.

Download Full-text

Personalized 3-Gene Panel for Prostate Cancer Target Therapy

Current Issues in Molecular Biology ◽

10.3390/cimb44010027 ◽

2022 ◽

Vol 44 (1) ◽

pp. 360-382

Author(s):

Sanda Iacobas ◽

Dumitru Andrei Iacobas

Keyword(s):

Prostate Cancer ◽

Normal Tissue ◽

Experimental Validation ◽

Target Therapy ◽

Experimental Manipulation ◽

Expression Level ◽

Individual Gene ◽

Expression Variability ◽

Master Regulators ◽

Expression Control

Many years and billions spent for research did not yet produce an effective answer to prostate cancer (PCa). Not only each human, but even each cancer nodule in the same tumor, has unique transcriptome topology. The differences go beyond the expression level to the expression control and networking of individual genes. The unrepeatable heterogeneous transcriptomic organization among men makes the quest for universal biomarkers and “fit-for-all” treatments unrealistic. We present a bioinformatics procedure to identify each patient’s unique triplet of PCa Gene Master Regulators (GMRs) and predict consequences of their experimental manipulation. The procedure is based on the Genomic Fabric Paradigm (GFP), which characterizes each individual gene by the independent expression level, expression variability and expression coordination with each other gene. GFP can identify the GMRs whose controlled alteration would selectively kill the cancer cells with little consequence on the normal tissue. The method was applied to microarray data on surgically removed prostates from two men with metastatic PCas (each with three distinct cancer nodules), and DU145 and LNCaP PCa cell lines. The applications verified that each PCa case is unique and predicted the consequences of the GMRs’ manipulation. The predictions are theoretical and need further experimental validation.

Download Full-text

Predictive and Prognostic Role of Lipocalin-2 Expression in Prostate Cancer and Its Association with Gleason Score

Prostate Cancer ◽

10.1155/2021/8836043 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

M. Hakan Ulusoy ◽

Yalcin Cirak ◽

Yasemen Adali

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Progression Free Survival ◽

Expression Level ◽

Lipocalin 2 ◽

Prognostic Role ◽

Kaplan Meier ◽

Docetaxel Treatment ◽

Castrate Resistant

Lipocalin-2 has an important role in tumor progression, invasion, and metastasis. However, its role in prostate cancer remains unclear. The objective of this study is to determine the expression level of lipocalin-2 in human prostate cancer tissues and to evaluate the relationship between its expression level and clinicopathologic parameters including response to docetaxel treatment, Gleason score, progression-free survival (PFS), and overall survival (OS). We retrospectively analyzed paraffin-embedded tissue sections from 33 metastatic castrate-resistant prostate cancer (mCRPC) patients whose clinical outcomes had been tracked after docetaxel treatment. The expression status of lipocalin-2 was defined by immunohistochemistry (IHC) using the anti-lipocalin-2 antibody. Lipocalin-2 was highly expressed in 36% of the examined specimens. There was no significant correlation between high lipocalin-2 expression and docetaxel response ( p : 0.09 ). High lipocalin-2 expression was signiﬁcantly associated with a higher Gleason score ( p = 0.027 ). Kaplan–Meier survival analysis failed to show a significant correlation between expression levels of lipocalin-2 and both OS and PFS although patients with high lipocalin-2 levels had a numerically shorter PFS and OS time compared to patients with low levels. Consequently, it is clear that further studies are needed to evaluate the predictive and prognostic role of lipocalin-2 in prostate cancer patients.

Download Full-text