Epigenetic Modifications in Prostate Cancer Metastasis and Microenvironment.

The gradual evolution of prostate tissue from benign tumor to malignant lesion or distant metastasis is driven by intracellular epigenetic changes and the tumor microenvironment remodeling. With the continuous study of epigenetic modifications, these tumor-driving forces are being discovered and are providing new treatments for cancer. Here we introduce the classification of epigenetic modification and highlight the role of epigenetic modification in tumor remodeling and communication of the tumor microenvironment.

Research on a Super-Resolution and Low-Complexity Positioning Algorithm Using FMCW Radar Based on OMP and FFT in 2D Driving Scene.

Multitarget positioning technology, such as FMCW millimeter-wave radar, has broad application prospects in autonomous driving and related mobile scenarios. However, it is difficult for existing correlation algorithms to balance high resolution and low complexity, and it is also difficult to ensure the robustness of the positioning algorithm using an aging antenna. This paper proposes a super-resolution and low-complexity positioning algorithm based on the orthogonal matching pursuit algorithm that can achieve more accurate distance and angle estimation for multiple objects in a low-SNR environment. The algorithm proposed in this paper improves the resolving power by two and one orders of magnitude, respectively, compared to the classical FFT and MUSIC algorithms in the same signal-to-noise environment, and the complexity of the algorithm can be reduced by about 25-30%, with the same resolving power as the OMP algorithm. Based on the positioning algorithm proposed in our paper, we use the PSO algorithm to optimize the arrangement of an aging antenna array so that its angle estimation accuracy is equivalent to that observed when the antenna is intact, improving the positioning algorithm's robustness. This paper also further realizes the use of the proposed algorithm and a single-frame intermediate frequency signal to estimate the position angle information of the object and obtain its motion trajectory and velocity, verifying the proposed algorithm's estimation ability when it comes to these qualities in a moving scene. Furthermore, this paper designs and carries out simulations and experiments. The experimental results verify that the positioning algorithm proposed in this paper can achieve accuracy, robustness, and real-time performance in autonomous driving scenarios.

RBM3 suppresses stemness remodeling of prostate cancer in bone microenvironment by modulating N6-methyladenosine on CTNNB1 mRNA.

Bone metastasis is the most happened metastatic event in prostate cancer (PCa) and needs a large effort in treatment. When PCa metastasizes to the bone, the new microenvironment can induce the epigenome reprogramming and stemness remodeling of cancer cells, thereby increasing the adaptability of cancer cells to the bone microenvironment, and this even leads to the occurrence of secondary tumor metastasis. Our group has previously found that RNA binding motif 3 (RBM3) affects the stem cell-like properties of PCa by interfering with alternative splicing of CD44. However, whether RBM3, as a stress-response protein, can resist microenvironmental remodeling of PCa particularly in bone metastasis remains unknown. By co-culturing PCa cells with osteoblasts to mimic PCa bone metastases, we found that RBM3 upregulates the N6-methyladenosine (m6A) methylation on the mRNA of catenin beta 1 (CTNNB1) in a manner dependent on methyltransferase 3 (METTL3), an N6-adenosine-methyltransferase complex catalytic subunit. Consequently, this modification results in a decreased stability of CTNNB1 mRNA and a followed inactivation of Wnt signaling, which ultimately inhibits the stemness remodeling of PCa cells by osteoblasts. Thus, the present study may extend our understanding of the inhibitory role of RBM3 on particularly bone metastasis of PCa.

Research progress of m6A methylation in prostate cancer.

N6-methyladenosine (m6A) is a ubiquitous RNA modification in mammals. This modification is "written" by methyltransferases and then "read" by m6A-binding proteins, followed by a series of regulation, such as alternative splicing, translation, RNA stability, and RNA translocation. At last, the modification is "erased" by demethylases. m6A modification is essential for normal physiological processes in mammals and is also a very important epigenetic modification in the development of cancer. In recent years, cancer-related m6A regulation has been widely studied, and various mechanisms of m6A regulation in cancer have also been recognized. In this review, we summarize the changes of m6A modification in prostate cancer and discuss the effect of m6A regulation on prostate cancer progression, aiming to profile the potential relevance between m6A regulation and prostate cancer development. Intensive studies on m6A regulation in prostate cancer may uncover the potential role of m6A methylation in the cancer diagnosis and cancer therapy.

Gypenoside L and Gypenoside LI Inhibit Proliferation in Renal Cell Carcinoma via Regulation of the MAPK and Arachidonic Acid Metabolism Pathways.

Renal cell carcinoma (RCC) has the highest mortality rate of all urological malignancies. Clear cell renal cell carcinoma (ccRCC) accounts for approximately 80% of all RCC cases and is often accompanied by the accumulation of lipid droplets. Growing evidence indicates that ccRCC is a metabolism-related disease. Gypenosides are commonly used for the clinical treatment of hyperlipidemia, and their antitumor activity has also been recognized. However, the potential inhibitory effects and mechanisms of action of gypenoside L (Gyp L) and gypenoside LI (Gyp LI) in ccRCC remain unclear. In this study, we confirmed that Gyp L and Gyp LI significantly inhibited proliferation and induced apoptosis in ccRCC cells in vitro. We performed network pharmacology and RNA-seq, and verified the results by Western blotting, RT-qPCR, and immunofluorescence experiments. Our results demonstrated that Gyp L and Gyp LI upregulate the expression of COX2 and downregulate the expression levels of cPLA2 and CYP1A1, resulting in reduced arachidonic acid and apoptosis. Gyp L and Gyp LI upregulated the protein levels of DUSP1, p-JUN, and p-JNK, and downregulated p-MEK1/2, p-ERK, and p-P38 levels. Moreover, gypenosides significantly inhibited tumor growth in vivo, and gypenosides significantly reduced cPLA2 and CYP1A1 expression. Furthermore, we performed absolute quantification of arachidonic acid (AA) content in ccRCC cells and tumor tissues by HPLC-MS, and found that the arachidonic acid content was significantly reduced after Gyp L, Gyp LI, and gypenoside intervention. In conclusion, our data suggest that Gyp L, Gyp LI, and gypenosides decrease the content of arachidonic acid in ccRCC cells and tumor tissues, but do not have cytotoxic effects on nude mice. Thus, Gyp L, Gyp LI, and total gypenosides extracted from Gynostemma pentaphyllum exhibited antitumor activities against ccRCC.

Gypenoside-Induced Apoptosis via the PI3K/AKT/mTOR Signaling Pathway in Bladder Cancer.

Gynostemma pentaphyllum (Thunb.) Makino (G. pentaphyllum) is a natural herbal drug that has been widely used to treat many diseases. The antitumor effects of G. pentaphyllum were first described in the illustrated catalog of plants. Gypenosides are the major active components of G. pentaphyllum, and they have been widely reported to possess antitumor effects in prostate cancer, gastric cancer, hepatocellular carcinoma, colon cancer, lung cancer, and breast cancer. However, research on the use of gypenoside in the treatment of bladder cancer has not been conducted. In this study, we explored the potential molecular mechanisms of gypenosides in the treatment of bladder cancer using network pharmacology and experimental validation. First, we used a network pharmacology-based method to identify both the effective components of gypenosides and the molecular mechanism underlying their antibladder cancer effects. The results were further confirmed by molecular docking, CCK8 and colony formation assays, and cell cycle and cell apoptosis analyses. Additionally, a mouse xenograft model of bladder cancer was used to investigate the antitumor effect of gypenosides in vivo. We identified 10 bioactive ingredients and 163 gene targets of gypenosides. Network exploration suggested that VEGFA, STAT3, and PI3KCA may be candidate agents for the antibladder cancer effect of gypenosides. In addition, analysis of the Kyoto Encyclopedia of Genes and Genomes pathway revealed that the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway may play a crucial role in the mechanism of action of gypenosides against bladder cancer. Molecular docking revealed that gypenosides combine well with PI3K, AKT, and mTOR. As expected, gypenosides displayed apoptosis-inducing properties in bladder cancer cells by inactivating the PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, gypenosides significantly (P < 0.05) inhibited the growth of bladder cancer cells in vivo. Mechanistically, gypenosides induced the apoptosis of bladder cancer cells via inactivation of the PI3K/AKT/mTOR signaling pathway.

Preoperative PI-RADS Version 2 scores helps improve accuracy of clinical nomograms for predicting pelvic lymph node metastasis at radical prostatectomy.

BACKGROUND: Lymph node invasion (LNI) is a strong adverse prognostic factor in prostate cancer (PCa). The purpose of this study was to evaluate the role of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) scores for estimating the risk of LN metastasis. The study also aimed to investigate the additional value of PI-RADSv2 scores when used in combination with clinical nomograms for the prediction of LNI in patients with PCa. METHODS: We retrospectively identified 308 patients who underwent multiparametric magnetic resonance imaging (mpMRI) and RP with pelvic lymph node dissection (PLND). Clinicopathological parameters and PI-RADSv2 scores were assessed. Univariate and multivariate logistic analyses were performed. The area under the receiver operating characteristic curves (AUCs) and decision curve analysis (DCA) were generated for assessing the incremental value of PI-RADSv2 scores combined with the Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms. RESULTS: Overall, 20 (6.5%) patients had LNI. At univariate analysis, all clinicopathological characteristics and PI-RADSv2 scores were significantly associated to LNI (p < 0.04). However, multivariate analysis revealed that only PI-RADSv2 scores and percentage of positive cores were independently significant (p ≤ 0.006). The PI-RADSv2 score was the most accurate predictor (AUC, 80.2%). The threshold of PI-RADSv2 score was 5, which provided high sensitivity (18/20, 90.0%) and negative predictive value (203/205, 99.0%). When PI-RADSv2 scores were combined with Briganti and MSKCC nomograms, the AUC value increased from 75.1 to 86.3% and from 79.2 to 87.9%, respectively (p ≤ 0.001). The DCA also demonstrated that the two nomograms plus PI-RADSv2 scores improved clinical risk prediction of LNI. CONCLUSIONS: The patients with a PI-RADSv2 score <5 were associated with a very low risk of LNI in PCa. Preoperative PI-RADSv2 scores could help improve the accuracy of clinical nomograms for predicting pelvic LN metastasis at radical prostatectomy.