Mitochondrial transplantation reduces lower limb ischemia-reperfusion injury by increasing skeletal muscle energy and adipocyte browning.

Recent studies have shown that mitochondrial transplantation can repair lower limb IRI, but the underlying mechanism of the repair effect remains unclear. In this study, we found that in addition to being taken up by skeletal muscle cells, human umbilical cord mesenchymal stem cells (hMSCs)-derived mitochondria were also taken up by adipocytes, which was accompanied by an increase in optic atrophy 1 (OPA1) and uncoupling protein 1. Transplantation of hMSCs-derived mitochondria could not only supplement the original damaged mitochondrial function of skeletal muscle, but also promote adipocyte browning by increasing the expression of OPA1. In this process, mitochondrial transplantation can reduce cell apoptosis and repair muscle tissue, which promotes the recovery of motor function in vivo. To the best of our knowledge, there is no study on the therapeutic mechanism of mitochondrial transplantation from this perspective, which could provide a theoretical basis.

Noncoding RNAs-based high KIF26B expression correlates with poor prognosis and tumor immune infiltration in colon cancer.

BACKGROUND: The protein kinesin family member 26B (KIF26B) is aberrantly expressed in various cancers. However, its particular role and association with tumor immune infiltration in colon adenocarcinoma (COAD) remain unclear. METHODS: All original data were downloaded directly from The Cancer Genome Atlas (TCGA), UCSC Xena, and Gene Expression Omnibus (GEO) databases and processed with R 3.6.3. KIF26B expression was analyzed using Oncomine, TIMER, TCGA, GEO databases, and our clinical specimens. KIF26B expression at the protein level was explored with Human Protein Atlas (HPA) database. The upstream miRNAs and lncRNAs were predicted by StarBase and validated using RT-qPCR. Correlation of KIF26B expression with the expression of immune-related or immune checkpoint genes and GSEA analysis of KIF26B-related genes were investigated via R software. Relationship of KIF26B expression with immune biomarkers or tumor immune infiltration levels was studied through GEPIA2 and TIMER databases. RESULTS: KIF26B was upregulated, and its overexpression was closely related to overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), T stage, N stage, and CEA levels in COAD. MIR4435-2HG/hsa-miR-500a-3p/KIF26B axis was identified as the promising regulatory pathway of KIF26B. KIF26B expression was positively correlated with immune-related genes, tumor immune infiltration, and biomarker genes of immune cells in COAD, and KIF26B-related genes were significantly enriched in macrophage activation-related pathways. Expression of immune checkpoint genes, including PDCD1, CD274, and CTLA4, was also closely related to KIF26B expression. CONCLUSIONS: Our results clarified that ncRNA-based increased KIF26B expression was associated with a worse prognosis and high tumor immune infiltration in COAD.

Blockage of MDM2-mediated p53 ubiquitination by yuanhuacine restrains the carcinogenesis of prostate carcinoma cells by suppressing LncRNA LINC00665.

Prostate cancer (PCa) is a challenging issue for men's health worldwide due to its uncontrolled proliferation and high metastatic potential. Increasing evidence has supported plant extracts and natural plant derivatives as promising antitumor therapy with less toxic side effects. Yuanhuacine is an active component isolated from Daphne genkwa and can effectively suppress the tumorigenesis of several cancers. However, its role in PCa remains unclear. In this study, yuanhuacine dose-dependently inhibited the proliferation and induced apoptosis of PCa cells. Moreover, yuanhuacine also restrained the invasion and migration of PCa cells. Mechanically, yuanhuacine decreased the ubiquitination and degradation of p53 protein, and ultimately increased p53 levels, which was regulated by inhibiting the phosphorylation and total protein levels of mouse double minute 2 (MDM2). Moreover, elevation of MDM2 reversed the suppressive efficacy of yuanhuacine in PCa cell viability, invasion, and migration. The network pharmacologic and bioinformatics analysis confirmed that MDM2 might be a common target of D. genkwa and LINC00665. Furthermore, yuanhuacine inhibited LINC00665 expression. Upregulation of LINC00665 reversed yuanhuacine-mediated inhibition in MDM2 protein expression and suppressed p53 levels by enhancing its ubiquitination in yuanhuacine-treated cells. Importantly, the inhibitory effects of yuanhuacine on cell viability and metastatic potential were offset after LINC00665 elevation. Together, the current findings highlight that yuanhuacine may possess tumor-suppressive efficacy by inhibiting LINC00665-mediated MDM2/p53 ubiquitination signaling. Therefore, this study indicates that yuanhuacine may be a promising candidate for the treatment of PCa.

Network and Experimental Pharmacology to Decode the Action of Wendan Decoction Against Generalized Anxiety Disorder.

Objective: The mechanism of Wendan Decoction (WDD) against Generalized Anxiety Disorder (GAD) was predicted by network pharmacology and validated by in vivo and in vitro experiments. Methods: The targets of WDD for the treatment of GAD were obtained by a search of online databases. Further, PPI network and KEGG enrichment were used to identify the key targets and pathways. Ultimately, these key targets and pathways were validated by in vivo experiments on GAD mice modeled by repeated restraint stress (RRS) and in vitro experiments on inflammatory factor stimulated BV-2 cells. Results: Through searching the databases, the 137 ingredients of WDD that correspond to 938 targets and 4794 targets related to GAD were identified. Among them, 569 overlapping targets were considered as the therapeutic targets of WDD for GAD. PPI analysis showed that the inflammation-related proteins IL-6, TNF, SRC and AKT1 were the key targets, and KEGG enrichment suggested that PI3K/AKT and MAPK signaling pathways were key pathways of WDD in the treatment of GAD. In vivo experiments, RRS mice exhibited abnormality in behavioristics in open field test (OFT) and elevated plus maze (EPM) and increases in serum corticosterone and the percentage of lymphocytes positive for IL-6 in peripheral blood. These abnormal changes can be reversed by WDD and the positive control drug paroxetine. In vitro experiments, WDD can inhibit IL-6 induced activation of PI3K/AKT and MAPK signaling pathways in BV2 cells, and suppress the ensuing release of inflammatory factors TNF-α, IL-1ß and PGE2, and showed a dose-dependent effect. Conclusion: WDD is able to resist GAD by relieving inflammatory response in peripheral and central system.

Carrier-Free Trehalose-Based Nanomotors Targeting Macrophages in Inflammatory Plaque for Treatment of Atherosclerosis.

Inducing autophagy of macrophages to improve abnormal lipid metabolism is an important way to treat atherosclerosis (AS). Yet, the current application of the mammalian target of rapamycin (mTOR)-dependent autophagy inducers is limited by the side effects and lack of targeting and low biological availability. Herein, a kind of nitric oxide (NO)-driven carrier-free nanomotor based on the reaction between trehalose (Tr, one of the mTOR-independent autophagy inducers), L-arginine (Arg), and phosphatidylserine (PS) is reported. The developed nanomotors use NO as the driving force, which is generated from the reaction between Arg and excessive reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) specifically presenting in the AS microenvironment. The high expression of ROS and iNOS in the AS site can be used as chemoattractants to induce chemotaxis behavior of the nanomotors to achieve the first-step targeting an AS plaque. Subsequently, the "eat me" signal sent by PS is exploited to precisely target to the macrophages in the AS plaque, realizing the plaque-macrophage-targeted effect by this step-by-step strategy. In vitro and in vivo results confirm that the introduction of the concept of carrier-free nanomotors has greatly improved the biological availability of trehalose (the dose can be reduced from 2.5 g kg-1 in previous reports to 0.01 g kg-1 in this work). Particularly, consumed ROS and the production of NO during the targeting process also play positive roles, in which the former regulates the M2 polarization of macrophages and the latter promotes the reconstruction of an endothelial barrier, which contributes to the multilink treatment of AS.

DDX10 promotes the proliferation and metastasis of colorectal cancer cells via splicing RPL35.

BACKGROUND: Colorectal cancer (CRC) has become the second deadliest cancer in the world and severely threatens human health. An increasing number of studies have focused on the role of the RNA helicase DEAD-box (DDX) family in CRC. However, the mechanism of DDX10 in CRC has not been elucidated. METHODS: In our study, we analysed the expression data of CRC samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, we performed cytological experiments and animal experiments to explore the role of DDX10 in CRC cells. Furthermore, we performed Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analyses. Finally, we predicted the interacting protein of DDX10 by LC-MS/MS and verified it by coimmunoprecipitation (Co-IP) and qPCR. RESULTS: In the present study, we identified that DDX10 mRNA was extremely highly expressed in CRC tissues compared with normal colon tissues in the TCGA and GEO databases. The protein expression of DDX10 was measured by immunochemistry (IHC) in 17 CRC patients. The biological roles of DDX10 were explored via cell and molecular biology experiments in vitro and in vivo and cell cycle assays. We found that DDX10 knockdown markedly reduced CRC cell proliferation, migration and invasion. Then, we constructed a PPI network with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA) showed that DDX10 was closely related to RNA splicing and E2F targets. Using LC-MS/MS and Co-IP assays, we discovered that RPL35 is the interacting protein of DDX10. In addition, we hypothesize that RPL35 is related to the E2F pathway and the immune response in CRC. CONCLUSIONS: In conclusion, provides a better understanding of the molecular mechanisms of DDX10 in CRC and provides a potential biomarker for the diagnosis and treatment of CRC.

Nitric oxide-driven nanomotors with bowl-shaped mesoporous silica for targeted thrombolysis.

Vein thrombosis is one of the most serious types of cardiovascular disease. During the traditional treatment, due to the excessive blood flow rate, the drug utilization rate at the thrombus site is low and the thrombolysis efficiency is poor. In this study, bowl-shaped silica nanomotors driven by nitric oxide (NO) are designed to target the thrombus surface by modifying arginine-glycine-aspartic acid (RGD) polypeptide, and simultaneously loading l-arginine (LA) and thrombolytic drug urokinase (UK) in its mesopore structure. LA can react with excessive reactive oxygen species (ROS) in the thrombus microenvironment to produce NO, thus promoting the movement of nanomotors to improve the retention efficiency and utilization rate of drugs in the thrombus site, and at the same time achieve the effect of eliminating ROS and reducing the oxidative stress of inflammatory endothelial cells. The loaded UK can dissolve thrombus quickly. It is worth mentioning that NO can not only be used as a power source of nanomotors, but also can be used as a therapeutic agent to stimulate the growth of endothelial cells and reduce vascular injury. This therapeutic agent based on nanomotor technology is expected to provide support for future research on thrombus treatment.

Na+/H+-Exchanger Family as Novel Prognostic Biomarkers in Colorectal Cancer.

BACKGROUND: The acidic characteristics of the tumor microenvironment (TME) are attributed to cancer cells' needs of metabolism which produce a large amount of H+. In order not to affect its own life activities, it needs to release H+ into the intercellular space through an efficient Na+/H+ exchanger. On account of the intestine whose physiological function is highly dependent on intestinal pH value, NHE family members may play a critical role in the occurrence and development of colorectal cancer (CRC). METHODS: TCGA, GEPIA2, ONCOMINE, UALCAN, STRING, TIMER, Cytoscape, TargetScan, ENCORI, LncBase v.2, DNMIVD, HPA, and CellMinerTM databases were used in our study. RESULTS: The mRNA expressions of SLC9A1, SLC9A2, SLC9A3, and SLC9A9 were evidently lower in COAD than in normal samples; however, the mRNA expressions of SLC9A5, SLC9A8, and SLC9B2 were higher. Besides, mRNA expressions of NHE family were extremely associated with clinicopathological features, tumor immune microenvironment and stemness score, DNA methylation, and patient prognosis in COAD. Moreover, we conjectured that NHE family may play a role through MAPK or ErbB signaling pathway according to the results of GO/KEGG enrichment analysis. At last, we found that NHE family members were key factors of various kinds of cancers. CONCLUSION: Our study indicated that NHE family represented new diagnostic and therapeutic targets for CRC, which could have important significance for the clinical treatment of CRC.

Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound.

Impaired wound healing is a major complication of diabetes and involves sustained inflammation and oxidative stress at the wound site. Here, we investigated the potential involvement of ferroptosis, a newly discovered form of cell death characterized by iron-dependent accumulation of lipid peroxides in the pathogenesis of diabetic wound healing. Fibroblasts and vascular endothelial cells exposed to high glucose concentrations in vitro contained elevated levels of reactive oxygen species (ROS), lipid peroxidation products, and ferroptosis-associated proteins and displayed reduced survival and migration. These effects of high glucose were all significantly reduced by treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Similarly, in a rat model of diabetes, direct application of Fer-1 to the wound site reduced the expression of oxidative stress and inflammation markers and accelerated wound healing via activation of the anti-inflammatory phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Our results implicate ferroptosis in wound healing and identify a potential new therapeutic target for difficult-to-treat diabetic wounds.NEW & NOTEWORTHY Ferroptosis-related characteristic changes were found in diabetic wound models. Inhibition of ferroptosis improved inflammatory infiltration of diabetic wounds. PI3K/AKT signal pathway was rescued by restraining of ferroptosis. Mitigation of ferroptosis in diabetic wound promoted the wound healing.

Oncological Outcome of Combining Cytoreductive Prostatectomy and Metastasis-Directed Radiotherapy in Patients with Prostate Cancer and Bone Oligometastases: A Retrospective Cohort Study.

BACKGROUND: The current standard of care for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to evaluate the efficacy and safety of a multimodal approach including local primary tumor therapy, metastasis-directed therapy (MDT), and hormonal therapy in patients with oligometastatic prostate cancer (PCa). METHODS: We reviewed data of patients with PCa and bone oligometastases at diagnosis treated in three institutions with ADT followed by cytoreductive surgery with or without metastases-directed radiotherapy. Oligometastases were defined as the presence of five or fewer metastatic lesions with the absence of visceral metastases. In this retrospective cohort study, 58 patients underwent cytoreductive radical prostatectomy and ADT. Of these, 26 patients (45%) received stereotactic body radiation therapy (SBRT) to all metastatic sites as a MDT. Oncological outcomes were analyzed using the Kaplan-Meier method. RESULTS: The median follow-up period was 46.2 months. Of the 58 patients, the 3-year castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival was 75.9% and 91.4%, respectively. Pre- or post-treatment predictive factors for progression to CRPC, including prostate-specific antigen (PSA) level at diagnosis ≥20 ng/mL, Gleason grade groups 5, clinical T stage cT3b-4, PSA nadir level of ≥0.05 ng/mL, and no MDT with SBRT, were significantly associated with progression to CRPC. Subgroup analysis showed that the MDT group had significantly better CRPC-free survival than the non-MDT group with Gleason grade groups 1-4 (HR=0.228; 95% CI= 0.056-0.926). A total of 3.4% of the patients had grade 2 acute genitourinary toxicities and 5.2% had grade 2 acute gastrointestinal toxicities. No late grade >2 adverse events were observed. CONCLUSION: This multi-center, retrospective cohort study revealed the feasibility of combining cytoreductive prostatectomy and metastasis-directed radiotherapy for newly-diagnosed oligometastatic PCa. This treatment strategy has the potential to delay the progression to CRPC.

Long non-coding RNA LINC01207 promotes prostate cancer progression by downregulating microRNA-1972 and upregulating LIM and SH3 protein 1.

Prostate cancer is a heritable and clinically heterogeneous cancer. Both long non-coding RNAs (lncRNAs) and microRNAs (miRs) have been implicated in the pathogenesis and development of prostate cancer. Analysis of microarray data indicated that the lncRNA LINC01207 was differentially expressed in prostate cancer. In silico analysis predicted the interaction between LINC01207 and miR-1972 as well as the interaction between miR-1972 and the mRNAs LIM and SH3 protein 1 (LASP1). Thus, we explored the role of LINC01207 and miR-1972 in the growth and progression of prostate cancer. Quantitative real-time polymerase chain reaction revealed that LINC01207 and LASP1 were highly expressed in prostate cancer, while miR-1972 expression was lower. The interaction among LINC01207, miR-1972, and LASP1 was confirmed by RNA-fluorescence in situ hybridization, RNA immunoprecipitation, and dual luciferase reporter assay, which verified that LINC01207 could bind to miR-1972 and downregulate miR-1972, and miR-1972 targeted LASP1 and negatively regulated its expression. Both in vitro and in vivo experiments found that silencing LINC01207 inhibited cell proliferation, migration, invasion and tumor formation and enhanced apoptosis in prostate cancer cells, suggesting that LINC01207 functioned as a tumor promoter in prostate cancer and that it may represent a novel therapeutic target.

DDX11-AS1exacerbates bladder cancer progression by enhancing CDK6 expression via suppressing miR-499b-5p.

PURPOSE: We investigated DDX11-AS1 effects on bladder cancer (BLCA) progression to identify a new potential therapeutic target for BLCA. METHODS: BLCA cases (n = 108) were enrolled. SW780 and J82 cells were transfected. Cell counting kit-8 (CCK-8) assay, wound healing assay and transwell migration assay was conducted. Cell cycle and apoptosis was detected by flow cytometry. Luciferase reporter assay was performed. DDX11-AS1, miR-499b-5p and CDK6 mRNA expression in tissues/cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). In vivo experiment was performed using nude mice. CDK6 and Ki67 proteins expression in cells and xenograft tumors were researched by Western blot and immunohistochemistry. RESULTS: Overexpressed DDX11-AS1 in BLCA was associated with poor outcome of patients. Compared with siCtrl group, SW780 and J82 cells of siDDX11-AS1 group had lower OD450 value (P < 0.01), less cells in S phase, more apoptosis cells (P < 0.05), higher relative wound width (P < 0.05) and less invasive cell number (P < 0.01). DDX11-AS1 promoted CDK6 expression via inhibiting miR-499b-5p. Compared with oe-DDX11-AS1 group, SW780 cells of oe-DDX11-AS1 + miR-499b-5p mimic group and oe-DDX11-AS1 + siCDK6 group had lower OD450 value (P < 0.01), less cells in S phrase, more apoptosis cells (P < 0.01), higher relative wound width (P < 0.05) and less invasive cell numbers (P < 0.01). DDX11-AS1 knockdown inhibited SW780 cells growth in vivo and suppressed CDK6 and Ki67 expression in xenograft tumors. CONCLUSION: DDX11-AS1 exacerbates BLCA progression by enhancing CDK6 expression via suppressing miR-499b-5p.

Is Extended Lesionectomy Needed for Patients with Cerebral Cavernous Malformations Presenting with Epilepsy? A Meta-Analysis.

OBJECTIVE: To determine whether extended lesionectomy is needed for patients with cerebral cavernous malformations presenting with epilepsy as compared with lesionectomy. METHODS: A literature search of PubMed, Embase, Web of Science, Clinical Trials and Cochrane Central Register of Controlled Trials was performed for pertinent English-language studies from 1967 to 2017. Eligible studies were selected according to uniform inclusion and exclusion criteria. RESULTS: Seven studies including 245 patients (107 receiving extended lesionectomy, 138 receiving lesionectomy) were selected. Meta-analysis and subgroup analyses were conducted to compare extended lesionectomy with lesionectomy. Pooled analysis demonstrated that seizure outcome was not statistically significantly improved in patients who underwent extended lesionectomy compared with lesionectomy (odds ratio = 0.77; 95% confidence interval, 0.39-1.51; P = 0.44; I2 = 15%). CONCLUSIONS: Extended lesionectomy does not contribute to better seizure control for patients with cerebral cavernous malformations with epilepsy. Resection of the lesion and surrounding hemosiderin is sufficient for patients with cerebral cavernous malformations presenting with epilepsy.

MicroRNA-590-5p regulates cell viability, apoptosis, migration and invasion of renal cell carcinoma cell lines through targeting ARHGAP24.

Renal cell carcinoma (RCC) is the leading cause of death in renal malignancies. MicroRNA-590-5p (miR-590-5p) is of great importance in the processes of many cancers regarding regulation of cancer cell invasion and proliferation. In our study, alternation of miR-590-5p expression in RCC cell lines through transfection with pre-miR-590-5p (up-regulation) or anti-miR-590-5p (down-regulation) was performed. Apoptosis and viability of RCC cell lines were measured by flow cytometry and CCK-8 analysis, respectively. Cell invasion and migration were estimated by Transwell assay. The association of miR-590-5p with ARHGAP24 expression was evaluated using luciferase assays, real-time PCR and western blot assay. The expressions of apoptosis and migration-related protein were also measured by western blotting. We found that pre-miR-590-5p transfection in Caki-2 and 786-O cells showed significant increases in cell viability, invasion and migration, which were accompanied by decreased cell apoptosis, while anti-miR-590-5p transfection obviously inhibited the cell viability, migration and invasion of Caki-2 and 786-O cells as well as induced apoptosis, compared with the negative control group. Furthermore, bioinformatics combined with luciferase reporter assays indicated that ARHGAP24 is directly targeted by miR-590-5p. ARHGAP24 overexpression in 786-O and Caki-2 cells phenocopied the effects of anti-miR-590-5p transfection along with enhanced expression of active Caspase-3 and Bax/Bcl-2 ratio as well as decreased expression of MMP-2 and MMP-9. These findings suggested that miR-590-5p/ARHGAP24 seems to function as a potentially beneficial target for RCC treatment.

Inhibitory member of the apoptosis-stimulating protein of p53 is overexpressed in bladder cancer and correlated to its progression.

Several lines of direct evidence show that inhibitory member of the apoptosis-stimulating protein of p53 (iASPP) has an important function in cancer progression. However, its expression pattern and relationship with clinical pathologic characteristics in bladder cancer (BC) have not been completely elucidated. In this study, firstly, samples from 3 patients with invasive BC were detected by liquid chromatography tandem mass spectrometry to confirm overexpression of iASPP in BC, then samples from patients with noninvasive and invasive BC were detected by real-time polymerase chain reaction, Western blot, and tissue microarry immunohistochemistry. The relationship between iASPP expression and various clinicopathological features was investigated. The results showed m-RNA and protein of iASPP were overexpressed in BC and the rate of iASPP-positive cells was positively correlated with Union for International Cancer Control-Tumor, Node, Metastases stage, histologic grade, lymph node metastasis and poor overall survive. The data demonstrate that iASPP is overexpressed in BC and promotes the malignancy of BC. iASPP maybe serve as a potential therapeutic target for BC.

Mass spectrometric detection combined with bioinformatic analysis identified possible protein markers and key pathways associated with bladder cancer.

We aimed to find possible protein markers and key pathways related to bladder cancer. In total, we extracted three bladder cancer tissues and three paracancerous tissues from Jiangsu Provincial People's Hospital Urology Department, and performed mass spectrometric detection with Q Exactive. Subsequently, we screened the differentially expressed proteins in the disease group and the normal group using the LIMMA package, and performed functional enrichment analyses using DAVID. Further, we constructed protein-protein interaction (PPI) networks with Cytoscape software, and analyzed modules with ClusterONE. In total, 165 differentially expressed proteins including 19 upregulated and 146 downregulated ones were obtained. ACTA2 (Actin, Alpha 2, Smooth Muscle, Aorta), ACTN1 (Actinin, Alpha 1), and VCL (Vinculin) were significant nodes with higher degrees in the PPI network. These three nodes were also hub nodes in module 2. Besides, functional enrichment analysis suggested that ECM-receptor interaction and focal adhesion were significant pathways, and these two pathways were also enriched in three network modules. In addition, ACTN1 and VCL were enriched in the focal adhesion pathway in module 2. Thus, ACTA2, ACTN1, and VCL may play important roles in bladder cancer progression and may be protein markers for this disease. The ECM-receptor interaction pathway and the focal adhesion pathway may be involved in the progression of bladder cancer. Furthermore, ACTN1 and VCL may play roles in bladder cancer development, partly via the focal adhesion pathway.

Artesunate Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor.

Prostatic cancer (PCa) is a leading cause of cancer related death in males and is often regarded as a kind of androgen-sensitive cancer. Artesunate (ART), a semi-synthetic derivative of the Chinese herb Artemisia annua, is such an anti-cancer agent. However, the effects and mechanism of ART on PCa cells remains unclear. The study aims to elaborate the mechanism of the involvement of androgen receptor (AR) in anti-prostatic cancer (PCa) of artesunate (ART). PCa cells 22rvl were used in vivo and in vitro, and the viability and apoptosis were conducted using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, respectively. Ectopic expressions of AR and DNA methyltransferase (DNMT) were detected in cells in overexpression or interference of AR or DNMT3b. ART dose-dependently suppressed tumor growth, inhibited cell viability, enhanced apoptosis, decreased AR expression, and increased the expression and the catalytic activity of DNMT3b in 22rv1 cells either in transplanted mice or in vitro. Furthermore, AR downregulated DNMT3b expression, and overexpression of AR or interference of DNMT3b could reverse ART-induced cytotoxicity and apoptosis in 22rvl cells, whereas overexpression of DNMT3b could not change the effect profiles of ART on the cells. The results indicated that ART suppressed tumor growth of prostatic cancer cells through AR-DNMT3b pathway, underlying ART will allow for the utilization of this Chinese therapeutic agent for the potential treatment of prostate cancer.

High Expression of Derlin-1 Is Associated with the Malignancy of Bladder Cancer in a Chinese Han Population.

Derlin-1 is overexpressed in various types of solid tumors and has an important function in cancer progression. However, its expression pattern in and association with the clinicopathological characteristics of human bladder cancer remain unclear. In the present study, 3 pairs of fresh samples of bladder cancer tissue and paracancerous tissue were first detected by liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to screen for differentially expressed proteins. Following bioinformatics analysis and assessments by qRT-PCR and western blotting, Derlin-1 was selected as a candidate protein and was then validated in samples from patients with bladder cancer by immunohistochemistry and western blotting. The results showed that the bladder cancer tissues exhibited higher levels of Derlin-1 expression than the paracancerous tissues (P < 0.05). Positive expression of Derlin-1 was significantly correlated with tumor stage, histological grade, and lymph node metastasis (P < 0.001) but was not correlated with other clinicopathological parameters including patient age (P = 0.758) and gender (P = 0.831). Besides, Derlin-1 was highly expressed in BC cell lines (um-uc-3 and T24), and the interference of Derlin-1 could reverse EMT progression, inhibit the tumor migration and invasion in T24 cells. Further, patients with positive Derlin-1 expression had shorter overall survival than those with negative expression (P < 0.001). Taken together, our results demonstrated that Derlin-1 was overexpressed in bladder cancer and was associated with the malignancy of bladder cancer.

LINC00312 inhibits the migration and invasion of bladder cancer cells by targeting miR-197-3p.

To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.