The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets.

Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated.

Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1.

Background: Hexokinase I (HK1) is highly expressed in a variety of malignancies, regulates glycolytic pathway in cancer cells, and thus considered to be one of the promising molecular targets for cancer therapy. Nonetheless, the development of a specific inhibitor against HK1 remains elusive.

Purpose: This study aims to elucidate the mechanism by which oridonin inhibits the proliferation and immune evasion of bladder cancer cells, specifically through the suppression of HK1.

HES1-mediated down-regulation of miR-138 sustains NOTCH1 activation and promotes proliferation and invasion in renal cell carcinoma.

Background: Although the aberrant activation of NOTCH1 pathway causes a malignant progression of renal cell carcinoma (RCC), the precise molecular mechanisms behind the potential action of pro-oncogenic NOTCH1/HES1 axis remain elusive. Here, we examined the role of tumor suppressive miR-138-2 in the regulation of NOTCH1-HES1-mediated promotion of RCC.

Methods: This study employed bioinformatics, xenotransplant mouse models, ChIP assay, luciferase reporter assay, functional experiments, real-time PCR and Western blot analysis to explore the mechanisms of miR-138-2 in the regulation of NOTCH1-HES1-mediated promotion of RCC, and further explored miR-138-2-containing combination treatment strategies.

CD133 prevents colon cancer cell death induced by serum deprivation through activation of Akt-mediated protein synthesis and inhibition of apoptosis.

During the early phase of tumorigenesis, primary malignant cells survive within a low nutrition environment caused by a poorly organized vascular system. Here, we sought to determine the functional significance of CD133 in the survival of cancer cells under nutrient-poor conditions. Knockdown and overexpression experiments demonstrated that CD133 suppresses colon cancer cell death induced by serum deprivation through activation of Akt-mediated anti-apoptosis and protein synthesis pathways.

Knockdown of E2F5 induces cell death via the TP53‑dependent pathway in breast cancer cells carrying wild‑type TP53.

E2F transcription factor 5 (E2F5) is a member of the E2F family of transcription factors, which are involved in regulation of various cellular processes, including cellular proliferation, apoptosis, differentiation and DNA damage response. Previously, we reported that E2F5 was aberrantly overexpressed in estrogen receptor (ER)‑negative breast cancer, especially in triple‑negative breast cancer (TNBC). In the present study, it was revealed that E2F5 gene silencing caused a significant reduction in the proliferation rate of breast cancer MCF7 (ER‑positive luminal‑type) and MDA‑MB‑231 (TNBC‑type) cells.

miR-489-3p inhibits proliferation and migration of bladder cancer cells through downregulation of histone deacetylase 2.

Since human bladder cancer (BC) is a common malignancy of the urinary system with poor prognosis, it is crucial to clarify the molecular mechanisms of BC development and progression. To the best of our knowledge, the current study demonstrated for the first time that miR-489-3p suppressed BC cell-derived tumor growth via the downregulation of histone deacetylase 2 (HDAC2). According to the results, expression levels of miR-489-3p were lower in BC tissues compared with corresponding normal tissues.

HIF-1α-dependent miR-424 induction confers cisplatin resistance on bladder cancer cells through down-regulation of pro-apoptotic UNC5B and SIRT4.

Background: Chemo-resistance of bladder cancer has been considered to be one of the serious issues to be solved. In this study, we revealed pivotal role of miR-424 in the regulation of CDDP sensitivity of bladder cancer cells.

Methods: The cytotoxicity of cisplatin and effect of miR-424 were assessed by flow cytometry and TUNEL.

TAp63 represses transcription of MYCN/NCYM gene and its high levels of expression are associated with favorable outcome in neuroblastoma.

TAp63 is an isoform of p63 gene, a p53 family gene that suppresses tumorigenesis via transcriptional regulation. TAp63 represses transcription of MYC oncogene in glioblastomas; however, its role in another MYC family gene, MYCN, has remained elusive. In this study, we showed that TAp63 repressed transcription of the MYCN gene in human cancer cells.

PTPRK suppresses progression and chemo-resistance of colon cancer cells via direct inhibition of pro-oncogenic CD133.

Receptor-type protein tyrosine phosphatase κ (PTPRK) is considered to be a candidate tumor suppressor. PTPRK dephosphorylates CD133, which is a stem cell marker; phosphorylated CD133 accelerates xenograft tumor growth of colon cancer cells through the activation of AKT, but the functional significance of this has remained elusive. In this study, we have demonstrated that knockdown of PTPRK potentiates the pro-oncogenic CD133-AKT pathway in colon cancer cells.

Silencing of promotes the epithelial-mesenchymal transition of skin squamous cell carcinoma-derived A431 cells.

Erythropoietin-producing hepatocellular (Eph) receptors and their ligand ephrins serve crucial roles in the interactions among epithelial cells. Eph receptor/ephrin signaling regulates cell functions, including proliferation, differentiation and migration, via these cell-cell interactions. We reported previously that EPHB2, a member of the Eph receptor family, was highly expressed in chemically induced cutaneous squamous cell carcinoma (cSCC) tissues in mice.

Histone deacetylase 2 is involved in DNA damage-mediated cell death of human osteosarcoma cells through stimulation of the ATM/p53 pathway.

Tumor suppressor p53 is a short-lived nuclear transcription factor, which becomes stabilized and activated in response to a wide variety of cellular stresses. Around 50% of human cancer tissues carry mutations, and certain mutations contribute to chemoresistance. In the present study, we found that histone deacetylase 2 (HDAC2) acts as a co-activator of tumor suppressor p53 and participates in the early molecular events following DNA damage.

Mapping of new skin tumor susceptibility loci by a phenotype-driven congenic approach.

As cancer susceptibility varies among mouse strains, mouse models are powerful tools for the identification of genes responsible for cancer development. Several cancer susceptibility loci have been mapped by genetic analysis using cancer-resistant and cancer-susceptible mouse strains. However, only a few corresponding genes for these loci have been identified, because most of the cancer susceptibility loci are low-penetrance alleles.

Hydrophobic structure of hairpin ten-ring pyrrole-imidazole polyamides enhances tumor tissue accumulation/retention in vivo.

To examine the hydrophobic structure of PI polyamides on tumor accumulation in vivo, PI polyamide-fluorescein conjugates 1-5 with the distinct number of N-methylimidazole (Im) units were synthesized. There existed an inverse relationship between the Im unit number of the compounds and their hydrophobicity. Compound 1 with one Im unit and 3 with three Im units accumulated and retained preferentially in tumor tissues compared to 5 with five Im units.

Impact of RUNX2 gene silencing on the gemcitabine sensitivity of p53‑mutated pancreatic cancer MiaPaCa‑2 spheres.

Recently, it has been well‑recognized that the response toward anticancer drugs differs between two‑ and three‑dimensional (2D and 3D) in vitro cancer cell growth models. In the present study, we have demonstrated that, similar to the conventional 2D monolayer culture systems which often lack in vivo physiological insights, RUNX2 gene silencing increases the gemcitabine (GEM) sensitivity of the 3D spheres generated from p53‑mutated pancreatic cancer MiaPaCa‑2 cells. According to our results, MiaPaCa‑2 cells, but not p53‑wild‑type pancreatic cancer SW1990 cells efficiently formed sphere structures in serum‑free sphere‑forming medium.

Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1): A potential biomarker for coronary artery disease in patients with obstructive sleep apnea.

Objective: Although severe obstructive sleep apnea (OSA) is an important risk factor for atherosclerosis-related diseases including coronary artery disease (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This study aimed to test our hypothesis that circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the prevalence of CAD in patients with OSA.

Methods: Eighty-two adults diagnosed with OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled.

Impact of RUNX2 on drug-resistant human pancreatic cancer cells with p53 mutations.

Background: Despite the remarkable advances in the early diagnosis and treatment, overall 5-year survival rate of patients with pancreatic cancer is less than 10%. Gemcitabine (GEM), a cytidine nucleoside analogue and ribonucleotide reductase inhibitor, is a primary option for patients with advanced pancreatic cancer; however, its clinical efficacy is extremely limited. This unfavorable clinical outcome of pancreatic cancer patients is at least in part attributable to their poor response to anti-cancer drugs such as GEM.

Depletion of runt-related transcription factor 2 (RUNX2) enhances SAHA sensitivity of p53-mutated pancreatic cancer cells through the regulation of mutant p53 and TAp63.

Suberoylanilide hydroxamic acid (SAHA) represents one of the new class of anti-cancer drugs. However, multiple lines of clinical evidence indicate that SAHA might be sometimes ineffective on certain solid tumors including pancreatic cancer. In this study, we have found for the first time that RUNX2/mutant p53/TAp63-regulatory axis has a pivotal role in the determination of SAHA sensitivity of p53-mutated pancreatic cancer MiaPaCa-2 cells.

Depletion of TFAP2E attenuates adriamycin-mediated apoptosis in human neuroblastoma cells.

Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system and accounts for approximately 15% of all pediatric cancer-related deaths. To newly identify gene(s) implicated in the progression of neuroblastoma, we investigated aberrantly methylated genomic regions in mouse skin tumors. Previously, we reported that TFAP2E, a member of activator protein-2 transcription factor family, is highly methylated within its intron and its expression is strongly suppressed in mouse skin tumors compared with the normal skin.

High Mutation Levels are Compatible with Normal Embryonic Development in Mlh1-Deficient Mice.

To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1-deficient lacZ-transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged.

Depletion of pro-oncogenic RUNX2 enhances gemcitabine (GEM) sensitivity of p53-mutated pancreatic cancer Panc-1 cells through the induction of pro-apoptotic TAp63.

Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation of p53 family TAp63-dependent cell death pathway. In this manuscript, we have extended our study to p53-mutated human pancreatic cancer Panc-1 cells. According to our present results, knockdown of mutant p53 alone had a marginal effect on GEM-mediated cell death of Panc-1 cells.

A route for a strong increase of critical current in nanostrained iron-based superconductors.

The critical temperature T and the critical current density J determine the limits to large-scale superconductor applications. Superconductivity emerges at T. The practical current-carrying capability, measured by J, is the ability of defects in superconductors to pin the magnetic vortices, and that may reduce T.

Origin of Pressure-induced Superconducting Phase in KxFe2-ySe2 studied by Synchrotron X-ray Diffraction and Spectroscopy.

Pressure dependence of the electronic and crystal structures of KxFe2-ySe2, which has pressure-induced two superconducting domes of SC I and SC II, was investigated by x-ray emission spectroscopy and diffraction. X-ray diffraction data show that compressibility along the c-axis changes around 12 GPa, where a new superconducting phase of SC II appears. This suggests a possible tetragonal to collapsed tetragonal phase transition.