Prostate Cancer Levels Research Articles

In Silico Design of Novel RGS2-Galpha-q Interaction Inhibitors with Anticancer Activity.

Regulators of G-protein signaling (RGS) are a family of approximately 30 proteins that bind to and deactivate the alpha subunits of G-proteins (Gα) by accelerating their GTP hydrolysis rates, which terminates G-protein coupled receptor (GPCR) signaling. Thus, RGS proteins are essential in regulating GPCR signaling, and most members are implicated as critical nodes in human diseases such as hypertension, depression, and others. Regulator of G-protein signaling 2 (RGS2), a member of the R4 family of RGS proteins, is overexpressed in many solid breast cancers, and its levels in prostate cancer significantly correlate with the metastatic stage and poor prognosis. We sought to develop RGS2 inhibitors as potential chemotherapeutic agents utilizing structure-based drug design approaches. Available structures of the RGS2-Gα complex were used to extract a pharmacophore model for searching chemical databases. Docking of identified hits to RGS2 as well as other RGS structures was used to screen the hits for potent and selective RGS2 inhibitors. Whole cell assays showed the top 10 ranking compounds, AJ-1-AJ-10, to inhibit RGS2-Gαq interactions. Differential scanning fluorimetry showed AJ-3 to bind RGS2 but not Gαq. All 10 compounds inhibited the growth of several RGS2 expressing cancers in cell culture assays. In addition, AJ-3 inhibited the migration of LNCaP prostate cancer cells in wound healing assays. This is the first group of RGS2 inhibitors identified by structure-based approaches and that show anticancer activity. These results highlight the potential RGS2 inhibitors have to be a new class of chemotherapeutic agents.

Correlation of testosterone and ESR2 in prostate cancer

Introduction: Prostate cancer (PCa), as the second most frequent cancer in males, has a significant challenge in determining differential diagnosis and prognosis of aggressive or non-aggressive prostate cancer. For functioning correctly, the prostate needs sex steroid hormones, which are also factors in the initiation and progression of carcinogenesis. Risk and Gleason score upgrading can be predicted by preoperative plasma testosterone levels in men with prostate cancer undergoing radical prostatectomy. Not only testosterone but estrogen also has roles in prostate cancer carcinogenesis. Estrogen Receptor 2 (ESR2) gene has been found to encode ER-β, which has an anti-proliferative effect on prostate tissue. This study aims to look up any correlation between testosterone and ESR2 in prostate cancer. Methods: This is an analytic cross-sectional study. We conducted a quantitative real-time polymerase chain reaction (qPCR) examination involving 15 benign prostate hyperplasia (BPH), 10 non-metastasized PCa, and 21 PCa patients for determining ESR2 expression from formalin-fixed paraffin-embedded (FFPE) prostate cancer tissue with known testosterone level in our institution. Data were analyzed using statistical tests with a significance of p <0.05. Results: The mean testosterone level and ESR2 expression are 785 ng/dl and 236.4 ng/dl 4.6 8.2, respectively, in BPH and PCa. Statistically, there was an inverse correlation between testosterone and ESR2 levels in prostate cancer (p<0.05). Conclusion: This study found lower testosterone correlates with ESR2 modulation.

Discovery of a novel natural compound, vitekwangin B, with ANO1 protein reduction properties and anticancer potential.

Background: Prostate cancer and non-small cell lung cancer (NSCLC) present significant challenges in the development of effective therapeutic strategies. Hormone therapies for prostate cancer target androgen receptors and prostate-specific antigen markers. However, treatment options for prostatic small-cell neuroendocrine carcinoma are limited. NSCLC, on the other hand, is primarily treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors but exhibits resistance. This study explored a novel therapeutic approach by investigating the potential anticancer properties of vitekwangin B, a natural compound derived from Vitex trifolia. Methods: Vitekwangin B was chromatographically isolated from the fruits of V. trifolia. ANO1 protein levels in prostate cancer and NSCLC cells were verified and evaluated again after vitekwangin B treatment. Results: Vitekwangin B did not inhibit anoctamin1 (ANO1) channel function but significantly reduced ANO1 protein levels. These results demonstrate that vitekwangin B effectively inhibited cancer cell viability and induced apoptosis in prostate cancer and NSCLC cells. Moreover, it exhibited minimal toxicity to liver cells and did not affect hERG channel activity, making it a promising candidate for further development as an anticancer drug. Conclusion: Vitekwangin B may offer a new direction for cancer therapy by targeting ANO1 protein, potentially improving treatment outcomes in patients with prostate cancer and NSCLC. Further research is needed to explore its full potential and overcome existing drug resistance challenges.

COL10A1 as a Prognostic Biomarker in Association with Immune Infiltration in Prostate Cancer.

The collagen type X alpha 1 (COL10A1) has recently been found to play an important role in the development and progression of cancer. However, the link between COL10A1 and the tumor immune microenvironment remains understood scantily. In the current study, the pan-cancer data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to investigate the expression mode, the clinical prognostic and diagnostic value of COL10A1 in different tumors. We used TCGA data to assess the correlations between COL10A1 and clinical symptoms of prostate cancer. The R packages "edgR" and "clusterProfiler" were used for differential expression gene and enrichment analysis of COL10A1. Immunohistochemistry was further employed to corroborate the expression of COL10A1 gene in prostate cancer. After that, we used TIMER to evaluate the pertinence of COL10A1 expression to immune infiltration level in prostate cancer. On the whole, COL10A1 was expressed at significantly higher levels in a variety of tumor tissues than in the corresponding normal tissues. Besides, significant correlations with tumor prognosis and relative exactitude in predicting tumors show that COL10A1 may be a probable prognostic and diagnostic biomarker of prostate cancer. In addition, the evidence indicates a significant correlation between COL10A1 and clinical symptoms of prostate cancer. Furthermore, the main molecular functions of COL10A1 included humoral immune response, complement activation, immunoglobulin, regulation of complement activation, and regulation of humoral immune response. Finally, we found that COL10A1 expression is positively correlated with enhanced macrophage and M2 macrophage infiltration in prostate cancer. The study indicates that COL10A1 might participate in M2 macrophage polarization in prostate cancer. COL10A1 might be an innovative biomarker to evaluate tumor microenvironment immune cell infiltration and prognosis in prostate cancer.

The Multifaceted Role of Osteopontin in Prostate Pathologies.

The prostate gland, located beneath the bladder and surrounding the proximal urethra in men, plays a vital role in reproductive physiology and sexual health. Despite its importance, the prostate is vulnerable to various pathologies, including prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Osteopontin (OPN), a versatile protein involved in wound healing, inflammatory responses, and fibrotic diseases, has been implicated in all three prostate conditions. The role of OPN in prostatic pathophysiology, affecting both benign and malignant prostate conditions, is significant. Current evidence strongly suggests that OPN is expressed at a higher level in prostate cancer and promotes tumor progression and aggressiveness. Conversely, OPN is primarily secreted by macrophages and foam cells in benign prostate conditions and provokes inflammation and fibrosis. This review discusses the accumulating evidence on the role of OPN in prostatic diseases, cellular sources, and potential roles while also highlighting areas for future investigations.

Sambucus nigra agglutinin as a supporter of docetaxel treatment in metastatic prostate cancer

Androgen deprivation therapy (ADT) has been the first treatment for advanced prostate cancer. Although 90% of patients initially respond to ADT, the disease inevitably progresses to castration-resistant prostate cancer (CRPC). Docetaxel was reported to provide significant benefit over other chemotherapeutics in prolonging survival in CRPC. Recently, other chemotherapeutics have been used in cases where docetaxel is insufficient or the patient develops resistance, but yet their efficacy is limited. For this reason, it is necessary to develop docetaxel-based therapy, reduce toxicity, increase treatment efficiency. It has been shown that the non-toxic plant lectin Sambucus nigra agglutinin (SNA) drives ovarian cancer cells to the apoptotic pathway. Increased sialic acid levels in prostate cancer have suggested that SNA lectin, which binds to glycan sialic acid residues, may also have an activating effect on the apoptotic pathway for prostate cancer. In order to evaluate this, docetaxel and SNA were applied to DU-145 cells alone and in combination. Arterwards XTT cytotoxicity test, RNA isolation, cDNA synthesis, gene expression analysis by real time PCR method were performed. In our study, SNA alone did not show any effect on prostate cancer cells whereas it increased the efficacy of docetaxel. Furthermore, our study showed for the first time that SNA + docetaxel has a synergistic effect on the increase in Bim and decrease in Drp1expressions. Based on the data obtained from the current study, it is thought that the use of the SNA + docetaxel combination in the treatment of metastatic prostate cancer will increase the treatment efficacy.

Critical Evaluation of Transcripts and Long Noncoding RNA Expression Levels in Prostate Cancer Following Radical Prostatectomy

Introduction: The clinical course of prostate cancer (PCa) is highly variable, ranging from indolent behavior to rapid metastatic progression. The Gleason score is widely accepted as the primary histologic assessment tool with significant prognostic value. However, additional biomarkers are required to better stratify patients, particularly those at intermediate risk. Methods: In this study, we analyzed the expression of 86 cancer hallmark genes in 171 patients with PCa who underwent radical prostatectomy and focused on the outcome of the 137 patients with postoperative R0-PSA0 status. Results: Low expression of the IGF1 and SRD52A, and high expression of TIMP2, PLAUR, S100A2, and CANX genes were associated with biochemical recurrence (BR), defined as an increase of prostate-specific antigen above 0.2 ng/mL. Furthermore, the analysis of the expression of 462 noncoding RNAs (ncRNA) in a sub-cohort of 39 patients with Gleason score 7 tumors revealed that high levels of expression of the ncRNAs LINC00624, LINC00593, LINC00482, and cd27-AS1 were significantly associated with BR. Our findings provide further evidence for tumor-promoting roles of ncRNAs in PCa patients at intermediate risk. The strong correlation between expression of LINC00624 and KRT8 gene, encoding a well-known cell surface protein present in PCa, further supports a potential contribution of this ncRNA to PCa progression. Conclusion: While larger and further studies are needed to define the role of these genes/ncRNA in PCa, our findings pave the way toward the identification of a subgroup of patients at intermediate risk who may benefit from adjuvant treatments and new therapeutic agents.

Subtype and prognostic analysis of immunogenic cell death-related gene signature in prostate cancer.

Immunogenic cell death (ICD) plays a vital role in tumor progression and immune response. However, the integrative role of ICD-related genes and subtypes in the tumor microenvironment (TME) in prostate cancer (PCa) remains unknown. The sample data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Memorial Sloan Kettering Cancer Center (MSKCC) prostate cancer-related databases. We first divided the subtypes based on ICD genes from 901 PCa patients and then identified the prognosis- related genes (PRGs) between different ICD subtypes. Subsequently, all the patients were randomly split into the training and test groups. We developed a risk signature in the training set by least absolute shrinkage and selection operator (LASSO)-Cox regression. Following this, we verified this prognostic signature in both the training test and external test sets. The relationships between the different subgroups and clinical pathological characteristics, immune infiltration characteristics, and mutation status of the TME were examined. Finally, the artificial neural network (ANN) and fundamental experiment study were constructed to verify the accuracy of the prognostic signature. We identified two ICD clusters with immunological features and three gene clusters composed of PRGs. Additionally, we demonstrated that the risk signature can be used to evaluate tumor immune cell infiltration, prognostic status, and an immune checkpoint inhibitor. The low-risk group, which has a high overlap with group C of the gene cluster, is characterized by high ICD levels, immunocompetence, and favorable survival probability. Furthermore, the tumor progression genes selected by the ANN also exhibit potential associations with risk signature genes. This study identified individuals with high ICD levels in prostate cancer who may have more abundant immune infiltration and revealed the potential effects of risk signature on the TME, immune checkpoint inhibitor, and prognosis of PCa.

Prognostic impact of kallikrein-related peptidase transcript levels in prostate cancer.

We aimed to study mRNA levels and prognostic impact of all 15 human kallikrein-related peptidases (KLKs) and their targets, proteinase-activated receptors (PARs), in surgically treated prostate cancer (PCa). Seventy-nine patients with localized grade group 2-4 PCas represented aggressive cases, based on metastatic progression during median follow-up of 11 years. Eighty-six patients with similar baseline characteristics, but no metastasis during follow-up, were assigned as controls. Transcript counts were detected with nCounter technology. KLK12 protein expression was investigated with immunohistochemistry. The effects of KLK12 and KLK15 were studied in LNCaP cells using RNA interference. KLK3, -2, -4, -11, -15, -10 and -12 mRNA, in decreasing order, were expressed over limit of detection (LOD). The expression of KLK2, -3, -4 and -15 was decreased and KLK12 increased in aggressive cancers, compared to controls (P < .05). Low KLK2, -3 and -15 expression was associated with short metastasis-free survival (P < .05) in Kaplan-Meier analysis. PAR1 and -2 were expressed over LOD, and PAR1 expression was higher, and PAR2 lower, in aggressive cases than controls. Together, KLKs and PARs improved classification of metastatic and lethal disease over grade, pathological stage and prostate-specific antigen combined, in random forest analyses. Strong KLK12 immunohistochemical staining was associated with short metastasis-free and PCa-specific survival in Kaplan-Meier analysis (P < .05). Knock-down of KLK15 reduced colony formation of LNCaP cells grown on Matrigel basement membrane preparation. These results support the involvement of several KLKs in PCa progression, highlighting, that they may serve as prognostic PCa biomarkers.

Upregulation of TLR5 indicates a favorable prognosis in prostate cancer.

Toll-like receptors (TLRs) are the key sensors of innate immunity for triggering immune responses against infections. TLRs are well known to be expressed and activated in innate immune cells, such as macrophage and dendritic cells, but we and others have found that some TLRs are also functional in epithelial cells. However, the role of an epithelial TLR in prostate cancer remains elusive. TLR5 expression in messenger RNA and protein level in prostate cancer was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). The activation of TLR5 signaling in epithelial cells was detected upon nuclear factor-κB activation by luciferase assay and western blot analysis, and proinflammatory cytokine activation by RT-qPCR. Distinguishing between the TLR5 and NLRC4 pathways, both recognizing flagellin, is determined by small interfering RNA and proinflammatory cytokine activation. The role of TLR5 in prostate cancer was analyzed by IHC and bioinformatics using a general and single-cell database. In the present study, we show that TLR5, among other TLRs, is exceedingly expressed in human prostate cancer cells. This cancer epithelial cell TLR5 functions to activate the TLR5 signaling pathway in human prostate cancer cells, as it does with innate immune cell TLR5. The bacterial protein flagellin induces a robust immune response in prostate cancer cells in a TLR5-dependent but NLRC4-independent manner. TLR5 is highly expressed in prostate cancer patient specimens, and high TLR5 expression in prostate cancer patients indicates a favorable prognosis. TLR5, as an innate immunity receptor, is a functional TLR in human prostate cancer epithelial cells. TLR5 plays an important role in prostate cancer development and is a new potential prognosis biomarker. TLR5 may represent a novel immunotherapy target against prostate cancer.

Comparative Study of Interleukin- 6 (Il-6) and Tumour Necrosis Factor Alpha (Tnf-Α) Levels in Prostate Cancer and Benign Prostatic Hyperplasia Subjects

Prostate cancer (PC) is an age-related malignancy that is very common in adult males with a very high morbidity and mortality rate worldwide. Chronic inflammation is thought to play a role in carcinogenesis. Pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tissue necrosis factor-α(TNF-α), have been implicated in the pathogenesis of prostate cancer (PC). Its diagnosis remains a challenge even with a combination of methods. Serum prostate specific antigen (Serum-PSA) is the universally accepted biomarker for PC detection. However, it is neither specific nor confirmatory. The aim of this study was to compare IL-6 and TNF-α levels in PC and benign prostatic hyperplasia (BPH) subjects. This cross-sectional, descriptive, non-random study involved 60 histologically diagnosed PC and 20 BPH subjects attending the Urology Clinic of the University of Port Harcourt Teaching Hospital (UPTH). The Enzyme Linked Immunosorbent Assay (ELISA) technique was used to assay the cytokines (IL-6 and TNF-α). From this study the peak incidence of PC and BPH subjects was observed at 60-69 years with a mean age of 68.31± 7.72 years and 66.5 ± 10.6 years respectively. The observed difference in IL-6 level in the PC and BPH subjects was not statistically significant (P = .6696). However, the mean serum TNF-α level (29.6 ± 3.2pg/ml) was significantly higher in PC subjects when compared to BPH subject levels (25.3 ± 4.7pg/ml) for TNF α. This study has shown that PC subjects have higher level TNF-α and as such it can serve as a differential marker for PC.

Comparison of serum iron, hemoglobin, ferritin and crp levels in prostate cancer patients with a control group Running title: Serum iron levels in prostate cancer

Comparison of serum iron, hemoglobin, ferritin and crp levels in prostate cancer patients with a control group Running title: Serum iron levels in prostate cancer

Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein

Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.

Assessment of Male Medical Students' Knowledge and Attitudes About Prostate Cancer and Screening at the University of Khartoum

Background: Prostate cancer (PC) is the most common cancer among men in Sudan. It was ranked fourth among all cancer treatment centers in Khartoum. This study aimed to assess knowledge and attitude toward PC among male medical students in their final and semifinal years at the University of Khartoum. Methods and Results: A descriptive cross-sectional online survey was conducted at the University of Khartoum (Faculty of Medicine) on semifinal and final-year male medical students from March 2022 until May 2022. Data were collected from medical students, using a standardized, pretested, coded questionnaire that contained close-ended questions. The questionnaire was distributed online to the medical students using Google Forms. Knowledge levels were determined using 10 questions on risk factors, signs and symptoms, prevention, treatment, and complications of PC. A total of 131 participants received questionnaires, and the response rate was 100%. The results are presented in chronological order in the way they were analyzed, starting with sociodemographic characteristics of the participants, sources of information on PC, knowledge levels (low, medium, and high) of PC, and attitude levels (positive, negative) relating to the year of study. All medical students in the last 2 years have heard about PC, and medical students overwhelmingly (88.5%) believe that early detection of PC through screening improves survival. Almost all the respondents in our study indicated their willingness to go for PC screening (87.8%), and the rest of the respondents’ attitudes about the importance of PC and treatment were positive. Conclusion: Most students have sufficient knowledge about prostate cancer, its risk factors, complications, and treatment. Medical students are an important population in studying the determinants of screening for prostate cancer.

Discovery of Lipid Metabolism-Related Genes for Predicting Tumor Immune Microenvironment Status and Prognosis in Prostate Cancer.

Background Reprogramming of lipid metabolism is closely associated with tumor development, serving as a common and critical metabolic feature that emerges during tumor evolution. Meanwhile, immune cells in the tumor microenvironment also undergo aberrant lipid metabolism, and altered lipid metabolism also has an impact on the function and status of immune cells, further promoting malignant biological behavior. Consequently, we focused on lipid metabolism-related genes for constructing a novel prognostic marker and evaluating immune status in prostate cancer. Methods Information about prostate cancer patients was obtained from TCGA and GEO databases. The NMF algorithm was conducted to identify the molecular subtypes. The least absolute shrinkage and selection operator (Lasso) regression analysis was applied to establish a prognostic risk signature. CIBERSORT algorithm was used to calculate immune cell infiltration levels in prostate cancer. External clinical validation data were used to validate the results. Results Prostate cancer samples were divided into two subtypes according to the NMF algorithm. A six-gene risk signature (PTGS2, SGPP2, ALB, PLA2G2A, SRD5A2, and SLC2A4) was independent of prognosis and showed good stability. There were significant differences between risk groups of patients with respect to the infiltration of immune cells and clinical variables. Response to immunotherapy also differed between different risk groups. Furthermore, the mRNA expression levels of the signature genes were verified in tissue samples by qRT-PCR. Conclusion We constructed a six-gene signature with lipid metabolism in prostate cancer to effectively predict prognosis and reflect immune microenvironment status.

Cirsilineol Inhibits the Proliferation of Human Prostate Cancer Cells by Inducing Reactive Oxygen Species (ROS)-Mediated Apoptosis

Cirsilineol has been reported to exhibit anticancer effects against several human cancer cell lines. The present study was designed to evaluate the anticancer effects of cirsilineol against the human DU-145 prostate cancer cells. The results showed that cirsilineol suppressed the proliferation of DU-145 cancer cells in a dose-dependent manner with minimal cytotoxic effects against the normal cells. The IC50 of cirsilineol was found to be 7 μM and 110 μM against prostate cancer DU-145 and normal HPrEC prostate cells, respectively. Acridine orange and ethidium bromide (AO/EB) staining showed that cirsilineol induced apoptosis in DU-145 prostate cancer cells. The Annexin V/PI staining further confirmed the induction of apoptosis in DU-145 cells. The western blot analysis showed that cirsilineol suppressed the expression of Bax and upregulated the expression of Bcl-2 in prostate cancer DU-145 cells. Moreover, cirsilineol caused a dose-dependent increase in reactive oxygen species (ROS) levels in prostate cancer. Wound healing and Transwell assays showed that cirsilineol inhibits migration and invasion of DU-145 prostate cancer cells. Summing up, the results suggest that cirsilineol suppresses the proliferation of prostate cancer cells and may prove to be a beneficial lead molecule for the development of chemotherapy for prostate cancer.

Lutetium-177 Prostate-Specific Membrane Antigen Therapy: A Practical Review

Prostate-specific membrane antigen is a transmembrane protein found predominately on prostate epithelium and is expressed at high levels in prostate cancer. In this review, we discuss the background, clinical data, patient selection, side effects, and necessary resources to deliver lutetium-177 prostate-specific membrane antigen in the research setting, or as standard of care if approved by the United States Food and Drug Administration. Targeted radionuclide therapeutics require understanding of fundamental principles of radiobiology and physics, and radiation oncologists and medical physicists are well-suited to play an integral role in their delivery and treatment response monitoring as key components of a multidisciplinary care team.

Evaluation of Interaction of Some Quinolone Derivatives on RSK-4 Using a Theoretical Model

Prostate cancer is one of the leading causes of death among men worldwide; Some data suggest that ribosomal S6 p90 kinase (RSK 1-4), which belongs to the group of highly conserved Ser/Thr kinases, has been related to an increase in prostate cancer levels. For this reason, the aim of this study was to evaluate the theoretical interaction of some quinolone derivatives (compounds 1-19) with RSK-4 using 6rv2 protein and RSK-14 inhibitor (LJH685) in a docking model. The results showed that some quino

Hsa_circ_0074032 promotes prostate cancer progression through elevating homeobox A1 expression by serving as a microRNA-198 decoy.

It has been reported that circular RNA hsa_circ_0074032 (circ_0074032) has a higher level in prostate cancer (PCa) tissues. However, the role and regulatory mechanism of circ_0074032 in PCa are still unknown. Circ_0074032 was overexpressed in PCa, and high circ_0074032level was associated with worse PCa-related prognosis. Functionally, circ_0074032silencing decreased xenograft tumour growth in vivo and induced cell apoptosis, curbed cell proliferation, migration and invasion in PCa cells in vitro. Furthermore, circ_0074032 was identified as a miR-198 decoy, and miR-198 inhibition abolished circ_0074032silencing-mediated effects on PCa cell proliferation, apoptosis, migration and invasion. In addition, miR-198 directly targeted homeobox A1 (HOXA1), and HOXA1 weakened miR-198mimic-mediated impacts on PCa cell malignant phenotypes. Importantly, circ_0074032 regulated HOXA1 expression by sponging miR-198. Our findings uncovered a novel mechanism by which circ_0074032 promoted PCa progression via elevating HOXA1 expression through acting as a miR-198sponge, providing a mechanism for circ_0074032 to affect the development of PCa.

Role of BCAR4 in prostate cancer cell autophagy.

BackgroundIncreased autophagy of prostate cancer (PC) cells contributes to their resistance to chemotherapy. Recently, we reported that a long non-coding RNA (lncRNA)—breast-cancer anti-estrogen resistance 4 (BCAR4)—is highly expressed in PC and contributes to castration resistance through activation of GLI2 signaling. However, the role of BCAR4 in the regulation of PC cell autophagy is unknown and is the subject of the current study.MethodsBCAR4 and Beclin-1 levels and the alteration in autophagy pathway genes were assessed in PC using a public database and in our own clinical specimens. The correlation between BCAR4 and Beclin-1 levels in PC and PC cell lines was determined and their regulatory relationship was assessed by overexpression and knockout assay. The final effect on autophagy was measured by microtubule-associated protein 1A/1B-light chain 3 (LC3) levels. The mechanism that underlies the control of Beclin-1 by BCAR4 was analyzed by cancer database and gain-of-function and loss-of-function approaches.ResultsBCAR4 and Beclin-1 were both upregulated in PC and were positively correlated. BCAR4 directly activated Beclin-1 at transcriptional level, which subsequently increased the ratio of LC3 II to LC3I to augment PC cell autophagy. Beclin-1 did not control levels of BCAR4. Mechanically, BCAR4 and Beclin-1 shared several targeting microRNAs, among which miR-15 and miR-146 appeared to be the mediators of the effects of BACR4 on Beclin-1.ConclusionsBCAR4 may enhance PC cell autophagy through altering miRNA-regulated Beclin-1 expression in PC.