Prostate Cancer Invasion Research Articles

Interstitial fluid flow contributes to prostate cancer invasion and migration to bone; study conducted using a novel horizontal flow bioreactor

Prostate cancer bone metastasis is the leading cause of cancer-related mortality in men in the United States, causing severe damage to skeletal tissue. The treatment of advanced-stage prostate cancer is always challenging due to limited drug treatment options, resulting in low survival rates. There is a scarcity of knowledge regarding the mechanisms associated with the effects of biomechanical cues by the interstitial fluid flow on prostate cancer cell growth and migration. We have designed a novel bioreactor system to demonstrate the impact of interstitial fluid flow on the migration of prostate cancer cells to the bone during extravasation. First, we demonstrated that a high flow rate induces apoptosis in PC3 cells via TGF-β1 mediated signaling; thus, physiological flow rate conditions are optimum for cell growth. Next, to understand the role of interstitial fluid flow in prostate cancer migration, we evaluated the migration rate of cells under static and dynamic conditions in the presence or absence of bone. We report that CXCR4 levels were not significantly changed under static and dynamic conditions, indicating that CXCR4 activation in PC3 cells is not influenced by flow conditions but by the bone, where CXCR4 levels were upregulated. The bone-upregulated CXCR4 levels led to increased MMP-9 levels resulting in a high migration rate in the presence of bone. In addition, upregulated levels of α v β 3 integrins under fluid flow conditions contributed to an overall increase in the migration rate of PC3 cells. Overall, this study demonstrates the potential role of interstitial fluid flow in prostate cancer invasion. Understanding the critical role of interstitial fluid flow in promoting prostate cancer cell progression will enhance current therapies for advanced-stage prostate cancer and provide improved treatment options for patients.

Status of 18F-PSMA-1007-PET/CT compared with multiparametric MRI in preoperative evaluation of prostate cancer.

Treatment of primary prostate cancer extremely depends on preoperative stage. The role of 18F-1007-PSMA-PET/CT in preoperative staging has not been well defined. Our aim was to compare the diagnostic performance of 18F-1007-PEMA-PET/CT, mpMRI, and mpMRI + PEMA-PET/CT in local progression and lymph node invasion of prostate cancer using histopathology as the gold standard. In this retrospective study, all patients with prostate cancer who underwent mpMRI and 18F-PSMA-1007-PET/CT before operation were included. The role of preoperative imaging was evaluated by predicting the sensitivity and specificity of EPE (extraprostatic extension), SVI (seminal vesicle invasion), and lymph node invasion results. Ultimately, 130 patients were included in this study. In the preoperative judgment of EPE and SVI, mpMRI + PSMA-PET/CT had higher sensitivity and specificity. When predicting lymph node metastasis, PSMA-PET/CT was the best choice. The accuracy of mpMRI + PSMA-PET/CT and PSMA-PET/CT in the T and N stages, respectively, was affected by the least factors. Based on the combined results of mpMRI and 18F-1007-PSMA-PET/CT, the accuracy of the preoperative judgment of prostatic capsule invasion can be improved, which may be conducive to developing intra-fascial technology while ensuring no tumor-touch isolation. PSMA-PET/CT has the advantages over mpMRI alone in terms of lymph node positivity. Compared with PSMA-PET/CT alone, the combined results can improve the sensitivity, but reduce specificity. Therefore, it is recommended to focus on PSMA-PET/CT to decide whether lymph node dissection should be performed.

ARPC5 is transcriptionally activated by KLF4, and promotes cell migration and invasion in prostate cancer via up-regulating ADAM17 : ARPC5 serves as an oncogene in prostate cancer.

Prostate cancer (PCa) is one of the most common cancers in men worldwide. Actin-related protein 2/3 complex subunit 5 (ARPC5) has been validated as a critical regulator in several kinds of human tumors. However, whether ARPC5 is implicated in PCa progression remains largely unknown. PCa specimens and PCa cell lines were obtained for detecting gene expressions using western blot and quantitative reverse transcriptase PCR (qRT-PCR). PCa cells transfected with ARPC5 shRNA or a disintegrin and metalloprotease 17 (ADAM17) overexpressed plasmids were harvested for assessing cell proliferation, migration and invasion by using cell counting kit-8 (CCK-8), colony formation and transwell assays, respectively. The interaction relationship between molecules was testified with chromatin immunoprecipitation and luciferase reporter assay. Xenograft mice model was conducted for confirming the role of ARPC5/ADAM17 axis in vivo. Upregulated ARPC5 was observed in PCa tissues and cells, as well as forecasted poor prognosis of PCa patients. Depletion of ARPC5 inhibited PCa cell proliferation, migration and invasion. Krüppel-like factor 4 (KLF4) was identified to be a transcriptional activator of ARPC5 via binding with its promoter region. Furthermore, ADAM17 served as a downstream effector of ARPC5. ADAM17 overexpression overturned ARPC5 knockdown-induced repressive impacts on PCa progression in vitro and in vivo. Collectively, ARPC5 was activated by KLF4 and upregulated ADAM17 to promote PCa progression, which might act as a promising therapeutic target and prognostic biomarker for PCa.

And Finally: Matters of Life and Death

And Finally: Matters of Life and Death

Trigred motif 36 regulates neuroendocrine differentiation of prostate cancer via HK2 ubiquitination and GPx4 deficiency.

Neuroendocrine prostate cancer (NEPC), the most lethal subtype of castration-resistant prostate cancer (PCa), may evolve from the neuroendocrine differentiation (NED) of PCa cells. However, the molecular mechanism that triggers NED is unknown. Trigred motif 36 (TRIM36), a member of the TRIM protein family, exhibits oncogenic or anti-oncogenic roles in various cancers. We have previously reported that TRIM36 is highly expressed to inhibit the invasion and proliferation of PCa. In the present study, we first found that TRIM36 was lowly expressed in NEPC and its overexpression suppressed the NED of PCa. Next, based on proteomic analysis, we found that TRIM36 inhibited the glycolysis pathway through suppressing hexokinase 2 (HK2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate. TRIM36 specifically bound to HK2 through lysine 48 (lys48)-mediated ubiquitination of HK2. Moreover, TRIM36-mediated ubiquitination degradation of HK2 downregulated the level of glutathione peroxidase 4 (GPx4), a process that contributed to ferroptosis. In conclusion, TRIM36 can inhibit glycolysis via lys48-mediated HK2 ubiquitination to reduce GPX4 expression and activate ferroptosis, thereby inhibiting the NED in PCa. Targeting TRIM36 might be a promising approach to retard NED and treat NEPC.

The Journal of Urology® Home Study Course 2023 Volume 209/210.

The Journal of Urology® Home Study Course 2023 Volume 209/210.

In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer

Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.

Procoxacin bidirectionally inhibits osteoblastic and osteoclastic activity in bone and suppresses bone metastasis of prostate cancer

BackgroundBone is the most common site of metastasis of prostate cancer (PCa). PCa invasion leads to a disruption of osteogenic-osteolytic balance and causes abnormal bone formation. The interaction between PCa and bone stromal cells, especially osteoblasts (OB), is considered essential for the disease progression. However, drugs that effectively block the cancer-bone interaction and regulate the osteogenic-osteolytic balance remain undiscovered.MethodsA reporter gene system was constructed to screen compounds that could inhibit PCa-induced OB activation from 631 compounds. Then, the pharmacological effects of a candidate drug, Procoxacin (Pro), on OBs, osteoclasts (OCs) and cancer-bone interaction were studied in cellular models. Intratibial inoculation, micro-CT and histological analysis were used to explore the effect of Pro on osteogenic and osteolytic metastatic lesions. Bioinformatic analysis and experiments including qPCR, western blotting and ELISA assay were used to identify the effector molecules of Pro in the cancer-bone microenvironment. Virtual screening, molecular docking, surface plasmon resonance assay and RNA knockdown were utilized to identify the drug target of Pro. Experiments including co-IP, western blotting and immunofluorescence were performed to reveal the role of Pro binding to its target. Intracardiac inoculation metastasis model and survival analysis were used to investigate the therapeutic effect of Pro on metastatic cancer.ResultsLuciferase reporter gene consisted of Runx2 binding sequence, OSE2, and Alp promotor could sensitively reflect the intensity of PCa-OB interaction. Pro best matched the screening criteria among 631 compounds in drug screening. Further study demonstrated that Pro effectively inhibited the PCa-induced osteoblastic changes without killing OBs or PCa cells and directly killed OCs or suppressed osteoclastic functions at very low concentrations. Mechanism study revealed that Pro broke the feedback loop of TGF-β/C-Raf/MAPK pathway by sandwiching into 14–3-3ζ/C-Raf complex and prevented its disassociation. Pro treatment alleviated both osteogenic and osteolytic lesions in PCa-involved bones and reduced the number of metastases of PCa in vivo.ConclusionsIn summary, our study provides a drug screening strategy based on the cancer-host microenvironment and demonstrates that Pro effectively inhibits both osteoblastic and osteoclastic lesions in PCa-involved bones, which makes it a promising therapeutic agent for PCa bone metastasis.Graphical

Europium (III) Incorporated Bovine Serum Albumin Stabilized Gold Nanoclusters as Fluorescent Probes for the Detection of Sarcosine, a Prostate Cancer Biomarker

AbstractA new fluorescent probe based on Eu (III) incorporated BSA‐AuNCs is developed for the selective sensing of sarcosine. Sarcosine is a simple non‐proteinogenic amino acid which is a clinical biomarker for prostate cancer. The non‐invasive sensing of a metabolite biomarker sarcosine for prostate cancer from urine sample was achieved through the developed Eu (III) incorporated BSA‐AuNCs probe. The developed sensor exhibited a good sensitivity and selectivity towards the metabolite sarcosine and observed no significant interference with other coexisting metabolites present in urine. The probe shows a very lower Limit of detection (LOD) of 0.177 mM and this probe can be developed for determining sarcosine on clinical basis. Considering its predominance and the pain associated invasive prostate cancer clinical examinations for the diagnosis, a non‐invasive diagnosis is of great need and significance.

The androgen receptor as a potential regulator of prostate cancer contractility.

Prostate cancer (PCa) is a common health hazard for men that displays androgen-dependent growth at early stages through signalling mediated by the Androgen Receptor (AR). This has inspired androgen deprivation therapy (ADT) to be the gold standard treatment; however, in later stages, PCa displays a transition to androgen-independence and loss of AR, accompanied by a drastic increase in invasiveness. Critically, both the loss of AR and ADT have been shown to induce PCa invasiveness by promoting the epithelial-to-mesenchymal transition (EMT) which has been associated with biophysical changes in other cell models. Indeed, during metastasis cancers cells change their biophysical properties (reduced cell stiffness, increased contractility) facilitating migration through crowded microenvironments. Given AR's essential role in mediating PCa progression, we suspect that AR signalling may also regulate mechanical transitions required for PC metastasis and directed cell migration. In this study we characterize PCa biophysics in response to changes in AR signalling and expression. First, we applied Traction Force Microscopy on the metastatic PCa cell line LNCaP (AR-positive) to quantify contractile changes from androgen deprivation and supplementation, observing a non-monotonic contractile response with increasing androgen dose. These results suggest that the androgen-induced biophysical response shifts depending on the androgen availability, a finding consistent with past reports demonstrating that distinct pathways depend on both androgen concentration and AR expression. Regarding the latter, we then evaluated how AR expression and activity (nuclear localization) affects PCa biophysics by quantifying the contractility of highly metastatic PC3 cells with and without AR expression under varying androgen concentrations. We find that cell contractility is positively correlated with AR nuclear localization in androgen-containing media, yet negatively correlated in androgen-deprived media. These results complement emerging trends suggesting AR may have an important mechanobiological role in PCa migration and metastasis.

Estrogens drive the endoplasmic reticulum-associated degradation and promote proto-oncogene c-Myc expression in prostate cancer cellsby androgen receptor/estrogen receptor signaling.

The tumorigenic properties of prostate cancer are regulated by advanced hormonal regulation-mediated complex molecular signals. Therefore, characterizing the regulation of these signal transduction systems is crucial for understanding prostate cancer biology. Recent studies have shown that endoplasmic reticulum (ER)-localized protein quality control mechanisms, including ER-associated degradation (ERAD) andunfolded protein response (UPR) signaling contribute to prostate carcinogenesis and to the development of drug resistance. It has also been determined that these systems are tightly regulated by androgens. However, the role of estrogenic signaling in prostate cancer and its effects on protein quality control mechanisms is not fully understood. Herein, we investigated the regulatory effects of estrogens on ERAD and UPR and their impacts on prostate carcinogenesis. We found that estrogens strongly regulated the ERAD components and IRE1⍺ branch of UPR by Er⍺/β/ARaxis. Besides,estrogenic signaling rigorously regulatedthe tumorigenicity of prostate cancer cells by promoting c-Myc expression and epithelial-mesenchymal transition (EMT). Moreover, estrogenic signal blockage significantly decreased the tumorigenic features of prostate cancer cells. Additionally, simultaneous inhibition of androgenic/estrogenic signals more efficiently inhibited tumorigenicity of prostate cancer cells, including proliferation, migration, invasion and colonial growth. Furthermore, computational-based molecular docking, molecular dynamics simulations and MMPBSA calculations supported the estrogenic stimulation of AR. Present findings suggested that ERAD components and IRE1⍺ signaling are tightlyregulated by estrogen-stimulated AR and Er⍺/β. Our data suggest that treatment approaches targeting the co-inhibition of androgenic/estrogenic signals may pave the way for new treatment approaches to be developed for prostate cancer. The present model of the impact of estrogens on ERAD and UPR signaling in androgen-sensitive prostate cancer cells.

Combination Treatment of a Phytochemical and a Histone Demethylase Inhibitor-A Novel Approach towards Targeting TGFβ-Induced EMT, Invasion, and Migration in Prostate Cancer.

Minimizing side effects, overcoming cancer drug resistance, and preventing metastasis of cancer cells are of growing interest in current cancer therapeutics. Phytochemicals are being researched in depth as they are protective to normal cells and have fewer side effects. Hesperetin is a citrus bioflavonoid known to inhibit TGFβ-induced epithelial-to-mesenchymal transition (EMT), migration, and invasion of prostate cancer cells. Targeting epigenetic modifications that cause cancer is another class of upcoming therapeutics, as these changes are reversible. Global H3K27me3 levels have been found to be reduced in invasive prostate adenocarcinomas. Combining a demethylase inhibitor and a known anti-cancer phytochemical is a unique approach to targeting cancer to attain the aforementioned objectives. In the current study, we used an H3K27 demethylase (JMJD3/KDM6B) inhibitor to study its effects on TGFβ-induced EMT in prostate cancer cells. We then gave a combined hesperetin and GSK-J4 treatment to the PC-3 and LNCaP cells. There was a dose-dependent increase in cytotoxicity and inhibition of TGFβ-induced migration and invasion of prostate cancer cells after GSK-J4 treatment. GSK-J4 not only induced trimethylation of H3K27 but also induced the trimethylation of H3K4. Surprisingly, there was a reduction in the H3K9me3 levels. GSK-J4 alone and a combination of hesperetin and GSK-J4 treatment effectively inhibit the important hallmarks of cancer, such as cell proliferation, migration, and invasion, by altering the epigenetic landscape of cancer cells.

Long non-coding RNA DNMBP-AS1 promotes prostate cancer development by regulating LCLAT1

Prostate cancer (PCa) is as a serious threat to male’s health around the world. Recent studies have indicated that long non-coding RNAs (lncRNAs) occupy an important position in various human cancers. However, the function and mechanism of lncRNA DNMBP antisense RNA 1 (DNMBP-AS1) in PCa is rarely investigated. RT-qPCR analysis was used to test gene expression. CCK-8, colony formation, EdU staining and transwell assays were conducted to assess the function of DNMBP-AS1 on PCa cell behaviors. RNA pull down, RIP and luciferase reporter assays were implemented to verify the mechanism of DNMBP-AS1. DNMBP-AS1 was obviously up-regulated in PCa cell lines. Functionally, DNMBP-AS1 knockdown weakened cell proliferation, migration and invasion of PCa. Mechanistically, DNMBP-AS1 sponged microRNA-6766-3p (miR-6766-3p) to regulate lysocardiolipin acyltransferase 1 (LCLAT1) expression. Furthermore, DNMBP-AS1 could stabilize LCLAT1 expression by recruiting ELAV like RNA binding protein 1 (ELAVL1). Consequently, rescue assays demonstrated that DNMBP-AS1 regulated PCa cell proliferation, migration and invasion through enhancing LCLAT1 expression. Collectively, we elucidated the function and regulatory mechanism of DNMBP-AS1 and provided the first evidence of DNMBP-AS1 as a driver for PCa.

Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer.

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.

Anticancer Effects of Morusin in Prostate Cancer via Inhibition of Akt/mTOR Signaling Pathway.

Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. The majority of PCa incidences eventually progress to castration-resistant PCa (CRPC), thereby establishing an urgent need for new effective therapeutic strategies. This study aims to examine the effects of morusin, a prenylated flavonoid isolated from Morus alba L., on PCa progression and identify the regulatory mechanism of morusin. Cell growth, cell migration and invasion, and the expression of EMT markers were examined. Cycle progression and cell apoptosis were examined using flow cytometry and a TUNEL assay, while transcriptome analysis was performed using RNA-seq with results being further validated using real-time PCR and western blot. A xenograft PCa model was used to examine tumor growth. Our experimental results indicated that morusin significantly attenuated the growth of PC-3 and 22Rv1 human PCa cells; moreover, morusin significantly suppressed TGF-[Formula: see text]-induced cell migration and invasion and inhibited EMT in PC-3 and 22Rv1 cells. Significantly, morusin treatment caused cell cycle arrest at the G2/M phase and induced cell apoptosis in PC-3 and 22Rv1 cells. Morusin also attenuated tumor growth in a xenograft murine model. The results of RNA-seq indicated that morusin regulated PCa cells through the Akt/mTOR signaling pathway, while our western blot results confirmed that morusin suppressed phosphorylation of AKT, mTOR, p70S6K, and downregulation of the expression of Raptor and Rictor in vitro and in vivo. These results suggest that morusin has antitumor activities on regulating PCa progression, including migration, invasion, and formation of metastasis, and might be a potential drug for CRPC treatment.

SEMA4A promotes prostate cancer invasion: involvement of tumor microenvironment.

Semaphorin 4A (SEMA4A) belonged to a family of membrane-bound proteins that were initially recognized as a kind of axon guidance factors in nervous system. It was preferentially expressed on immune cells and has been proven to play a prominent role in immune function and angiogenesis. In this study, we found that SEMA4A was highly expressed in prostate cancer (PCa) tissues and correlated with Gleason scores and distant metastasis. SEMA4A could induce Epithelial-mesenchymal transition (EMT) of PCa cells and consequently promote invasion by establishing a positive loop with IL-10 in stromal cells. In vivo experiments showed more dissemination in mice injected with SEMA4A-overexpressing cells in mouse models and both the number and size of lung metastases were significantly increased in SEMA4A-overexpressing tumors. SEMA4A depletion by genetic means prevents lung metastasis in PCa xenograft models. Our data suggest a crucial role of SEMA4A in PCa and blocking SEMA4A-IL-10 axis represents an attractive approach to improving therapeutic outcomes.

Diagnostic pitfalls: a case of prostate cancer and rectal cancer accompanied by prostate cancer invasion of the rectum

IntroductionCase of double primary cancer of the prostate and rectum is rare, prostate cancer involving the postoperative intestinal anastomotic mucosal tissue is even rarer.Case presentationWe report a case of rectal cancer discovered 1 year after a diagnosis of prostate cancer and a tumour in the postoperative anastomotic intestinal mucosal tissue involving prostatic adenocarcinoma at 1 year after the diagnosis of rectal cancer. Due to the poor differentiation of both prostate and rectal cancers, there are some pitfalls in the diagnosis of intestinal mucosal lesions at an anastomosis. The lack of an accurate diagnosis of a tumour in anastomosis intestinal mucosal tissue will affect treatment and patient survival.ConclusionsThe pathologists should have a detailed understanding of the patient's medical history and carefully observe the histopathological morphology and, if necessary, immunohistochemistry or other techniques should be used to assist in the pathological diagnosis and avoid both misdiagnosis and missed diagnosis.

CircEZH2E2 /E3 is a dual suppressor of miR363/miR708 to promote EZH2 expression and prostate cancer progression.

The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is overexpressed in a variety of malignancies including prostate cancer (PCa) and may play important roles in tumor progression. Gene copy number gains, enhanced transcription, and a few circRNAs have been reported to upregulate EZH2. It was not known whether EZH2 itself generates circRNAs that promote its own expression. We here report the identification of circEZH2E2/E3 that is derived from exons 2 and 3 of the EZH2 gene and overexpressed in PCa. We show that circEZH2E2/E3 functions as a dual inhibitor for both miR363 and miR708 that target the EZH2 3'UTR and CDS, respectively, resulting in the upregulation of EZH2 expression and hence the downregulation of EZH2-repressed genes (e.g., CDH1 and DAB2IP), and enhancement of PCa cell proliferation, migration, invasion, and xenograft PCa growth. Overexpression of circEZH2E2/E3 is significantly correlated with higher tumor grade, tumor progression, and unfavorable progression-free and disease-specific survival in PCa patients. These findings show a novel autoenhancing EZH2-circEZH2E2/E3 -miR363/miR708-EZH2 regulatory loop, by which circEZH2E2/E3 plays important roles in PCa tumorigenesis and progression by upregulating EZH2, and may have potential diagnostic, prognostic, and therapeutic uses in PCa management.

HLA-BAT1 alters migration, invasion and pro-inflammatory cytokines in prostate cancer.

Prostate cancer (PCa) accounts for more than 1 in 5 diagnoses and is the second cause of cancer-related deaths in men. Although PCa may be successfully treated, patients may undergo cancer recurrence and there is a need for new biomarkers to improve the prediction of prostate cancer recurrence and improve treatment. Our laboratory demonstrated that HLA-B-associated transcript 1 (BAT1) was differentially expressed in patients with high Gleason scores when compared to low Gleason scores. BAT1 is an anti-inflammatory gene but its role in PCa has not been identified. The objective of this study is to understand the role of BAT1 in prostate cancer. In vitro studies showed that BAT1 down-regulation increased cell migration and invasion. In contrast, BAT1 overexpression decreased cell migration and invasion. RT-PCR analysis showed differential expression of pro-inflammatory cytokines (TNF-α and IL-6) and cell adhesion and migration genes (MMP10, MMP13, and TIMPs) in BAT1 overexpressed cells when compared to BAT1 siRNA cells. Our in vivo studies demonstrated up-regulation of TNF-α, IL-6, and MMP10 in tumors developed from transfected BAT1 shRNA cells when compared to tumors developed from BAT1 cDNA cells. These findings indicate that BAT1 down-regulation modulates TNF-α and IL-6 expression which may lead to the secretion of MMP-10 and inhibition of TIMP2.

Retraction statement: Knockdown of lncRNA MNX1-AS1 suppresses cell proliferation, migration, and invasion in prostate cancer.

Retraction statement: Knockdown of lncRNA MNX1-AS1 suppresses cell proliferation, migration, and invasion in prostate cancer.