Downregulation of Circ-CEP128 Enhances the Paclitaxel Sensitivity of Cervical Cancer Through Regulating miR-432-5p/MCL1.

Chemoresistance is a common problem in cancer treatment, and circular RNA (circRNA) has been found to be associated with the progression of chemoresistance in cancer. However, the role and mechanism of circRNA centrosomal protein 128 (circ-CEP128) in the chemoresistance of cervical cancer (CC) are still unclear. The expression of circ-CEP128, microRNA (miR)-432-5p, and myeloid cell leukemia-1 (MCL1) was measured by quantitative real-time PCR.

ABCC5 facilitates the acquired resistance of sorafenib through the inhibition of SLC7A11-induced ferroptosis in hepatocellular carcinoma.

Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), and reducing sorafenib resistance is an important issue to be resolved for the clinical treatment of HCC. In the current study, we identified that ABCC5 is a critical regulator and a promising therapeutic target of acquired sorafenib resistance in human hepatocellular carcinoma cells. The expression of ABCC5 was dramatically induced in sorafenib-resistant HCC cells and was remarkably associated with poor clinical prognoses.

Calcium Channel Blocker Nifedipine Suppresses Colorectal Cancer Progression and Immune Escape by Preventing NFAT2 Nuclear Translocation.

Abnormal activation of calcium channels has been shown to play crucial roles in tumor occurrence and development. However, the role of inhibitors targeting calcium channels in tumor progression and immune regulation remains unclear, and their clinical applications are still limited. We show that nifedipine (NIFE), a calcium channel blocker, inhibits calcium influx to impair nuclear factor of activated T cell 2 (NFAT2) dephosphorylation, activation, and nuclear translocation, thus preventing transcriptional activation of downstream signaling molecules to suppress colorectal cancer (CRC) proliferation and metastasis.

LASP1 interacts with N-WASP to activate the Arp2/3 complex and facilitate colorectal cancer metastasis by increasing tumour budding and worsening the pattern of invasion.

LIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumour progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. As the major biological and pathological functions of LASP1 are accomplished by its LIM and SH3 domains via protein-protein interactions, a yeast two-hybrid system was employed to screen novel LASP1-interacting proteins.

Skp2 modulates proliferation, senescence and tumorigenesis of glioma.

Background: Gliomas represent the largest class of primary central nervous system neoplasms, many subtypes of which exhibit poor prognoses. Surgery followed by radiotherapy and chemotherapy has been used as a standard strategy but yielded unsatisfactory improvements in patient survival outcomes. The S-phase kinase protein 2 (Skp2), a critical component of the E3-ligase SCF complex, has been documented in tumorigenesis in various cancer types but its role in glioma has yet to be fully clarified.

Tumor-secreted dickkopf2 accelerates aerobic glycolysis and promotes angiogenesis in colorectal cancer.

Angiogenesis is a fundamental process that involves in tumor progression and metastasis. Vascular endothelial growth factor (VEGF) family and their receptors are identified as the most prominent regulators of angiogenesis. However, the clinical efficacy of anti-VEGF/VEGFR therapy is not ideal, prompting the needs to further understand mechanisms behind tumor angiogenesis.

Gut microbiota-stimulated cathepsin K secretion mediates TLR4-dependent M2 macrophage polarization and promotes tumor metastasis in colorectal cancer.

Metastasis is a complex process that requires the interaction between tumor cells and their microenvironment. As an important regulator of intestinal microenvironment, gut microbiota plays a significant role in the initiation and progression of colorectal cancer (CRC), but the underlying mechanisms remain elusive. In this study, a metastasis-related secretory protein cathepsin K (CTSK) was identified as a vital mediator between the imbalance of intestinal microbiota and CRC metastasis.

Cysteine-rich intestinal protein 1 suppresses apoptosis and chemosensitivity to 5-fluorouracil in colorectal cancer through ubiquitin-mediated Fas degradation.

Background: Cysteine-rich intestinal protein 1 (CRIP1) is highly expressed in human intestine and aberrantly expressed in several types of tumor. However, studies on CRIP1 are limited and its role on tumor development and progression remains controversial and elusive.

Methods: Immunohistochemistry was performed to evaluate the expression of CRIP1 in paired normal and colorectal tumor specimens, as well as colorectal cell lines.

A patent review of the ubiquitin ligase system: 2015-2018.

Ubiquitin-proteasome system (UPS) has been validated as a novel anticancer drug target in the past 20 years. The UPS contains two distinct steps: ubiquitination of a substrate protein by ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3), and substrate degradation by the 26S proteasome complex. The E3 enzyme is the central player in the ubiquitination step and has a wide range of specific substrates in cancer cells, offering great opportunities for discovery and development of selective drugs.

Inadequate ubiquitination-proteasome coupling contributes to myocardial ischemia-reperfusion injury.

The ubiquitin-proteasome system (UPS) degrades a protein molecule via 2 main steps: ubiquitination and proteasomal degradation. Extraproteasomal ubiquitin receptors are thought to couple the 2 steps, but this proposition has not been tested in vivo with vertebrates. More importantly, impaired UPS performance plays a major role in cardiac pathogenesis, including myocardial ischemia-reperfusion injury (IRI), but the molecular basis of UPS impairment remains poorly understood.

[Independent external verification of the nomograms for predicting lymph node metastasis in penile cancer].

Objective: To evaluate the two newly established nomograms for predicting lymph node metastasis in penile cancer based on the clinical data on a large cohort of patients.

Methods: We retrospectively studied the clinical data on 93 patients with penile cancer treated in the Center for Tumor Prevention and Treatment. Using the two recently established nomograms (Bhagat nomogram and Zhu nomogram), we predicted lymph node metastasis in the patients, analyzed the differences between prediction and the results of postoperative pathology, and compared the accuracy of prediction between the two nomograms with the receiver operating characteristic (ROC) curve and the area under the curve (AUC).

Inhibition of Proteasomal Deubiquitinase by Silver Complex Induces Apoptosis in Non-Small Cell Lung Cancer Cells.

Background/aims: The ubiquitin proteasome system (UPS) is responsible for the degradation of most intracellular proteins, and proteasomal deubiquitinases (DUBs) have recently been highlighted as novel anticancer targets. It is well documented that copper complexes can inhibit UPS function through targeting both 20S proteasome and proteasomal DUBs. The antineoplastic activities of silver complexes have received much attention, but the exact mechanisms are not fully elucidated.

Discovering proteasomal deubiquitinating enzyme inhibitors for cancer therapy: lessons from rational design, nature and old drug reposition.

The ubiquitin proteasome system has been validated as a target of cancer therapies evident by the US FDA approval of anticancer 20S proteasome inhibitors. Deubiquitinating enzymes (DUBs), an essential component of the ubiquitin proteasome system, regulate cellular processes through the removal of ubiquitin from ubiquitinated-tagged proteins. The deubiquitination process has been linked with cancer and other pathologies.

Histone deacetylase inhibitor AR-42 inhibits breast cancer cell growth and demonstrates a synergistic effect in combination with 5-FU.

AR-42 is a member of a novelly discovered class of phenylbutyrate-derived histone deacetylase inhibitors, and has a number of antitumor effects in a variety of tumor types; however, the role of AR-42 and its possible mechanisms have not been reported in the treatment of breast cancer. The aim of the present study was to investigate the antitumor effects of AR-42 and its associated mechanisms in breast cancer. MTT assays and colony formation assays were conducted to measure the proliferation of MCF-7 cells, and flow cytometry was used to analyze cell apoptosis.

Downregulation of RFX1 predicts poor prognosis of patients with small hepatocellular carcinoma.

Objective: Regulatory factor X1 (RFX1) deletion has been reported to be correlated with poor prognosis of some types of cancer. The present study aimed to investigate the prognostic value of RFX1 in HCC, especially in small hepatocellular carcinoma.

Methods: Immunohistochemical assay was used to investigate RFX1 expression in 221 HCC tissues and another validation cohort of 71 small HCC samples.

Perspectives on the recent developments with green tea polyphenols in drug discovery.

Increasing evidence has expanded the role of green tea from a traditional beverage to a source of pharmacologically active molecules with diverse health benefits. However, conclusive clinical results are needed to better elucidate the cancer-preventive and therapeutic effects of green tea polyphenols (GTPs). Areas covered: The authors describe GTPs' chemical compositions and metabolic biotransformations, and their recent developments in drug discovery, focusing on their cancer chemopreventive and therapeutic effects.

LASP1 promotes nasopharyngeal carcinoma progression through negatively regulation of the tumor suppressor PTEN.

LIM and SH3 protein 1 (LASP1) enhances tumor growth and metastasis in various cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we investigated the role of LASP1 in NPC and explored the underlying mechanisms in NPC. Clinically, overexpression of LASP1 is associated with tumor metastasis and poor prognosis of NPC patients.

[Discrimination and clinical value of plasma metabolomic profiles in multidrug resistant epithelial ovarian cancer].

To explore the alteration of plasma metabolomic profiles, screen the new serum markers of multidrug resistant epithelial ovarian cancer (EOC), and investigate the mechanism. The serum of 132 cases with cisplatin-resistant EOC, cisplatin-sensitive EOC, benign ovarian cyst and healthy donors were collected. Differentially plasma metabolic profiles were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4.

Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies.

Cadmium pyrithione suppresses tumor growth in vitro and in vivo through inhibition of proteasomal deubiquitinase.

The ubiquitin-proteasome system (UPS) is indispensable to the protein quality control in eukaryotic cells. Due to the remarkable clinical success of using proteasome inhibitors for clinical treatment of multiple myeloma, it is anticipated that targeting the UPS upstream of the proteasome step be an effective strategy for cancer therapy. Deubiquitinases (DUB) are proteases that remove ubiquitin from target proteins and therefore regulate multiple cellular processes including some signaling pathways altered in cancer cells.

Metal-based proteasomal deubiquitinase inhibitors as potential anticancer agents.

Deubiquitinases (DUBs) play an important role in protein quality control in eukaryotic cells due to their ability to specifically remove ubiquitin from substrate proteins. Therefore, recent findings have focused on the relevance of DUBs to cancer development, and pharmacological intervention on these enzymes has become a promising strategy for cancer therapy. In particular, several DUBs are physically and/or functionally associated with the proteasome and are attractive targets for the development of novel anticancer drugs.

Hinokitiol copper complex inhibits proteasomal deubiquitination and induces paraptosis-like cell death in human cancer cells.

The ubiquitin-proteasome system (UPS) plays a central role in the regulation of proteins that control cell growth and apoptosis and has therefore become an important target for anticancer therapy. Several constitutive subunits of the 19S proteasome display deubiquitinase (DUB) activity, suggesting that ubiquitin modification of proteins is dynamically regulated. Our study and others have shown that metal complexes, such as copper complexes, can induce cancer cell apoptosis through inhibiting 19S proteasome-associated DUBs and/or 20S proteasome activity.

Platinum pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via DUB inhibition-dependent caspase activation and Bcr-Abl downregulation.

Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. T315I Bcr-Abl is the most notorious point mutation to elicit acquired resistance to imatinib (IM), leading to poor prognosis. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance.