ENO1 deletion potentiates ferroptosis and decreases glycolysis in colorectal cancer cells via AKT/STAT3 signaling.

Colorectal cancer (CRC) is one of the most prevailing and lethal forms of cancer globally. α-enolase (ENO1) has been well documented to be involved in the progression and drug resistance of CRC. The present study was designed to specify the role of ENO1 in major events during the process of CRC and to introduce its latent functional mechanism. ENO1 expression was determined by western blot analysis. Extracellular acidification rates were assessed using an XF96 extracellular flux analyzer. Glucose uptake, lactic acid production, total iron levels and ferroptosis-related markers were examined with corresponding kits. A dichlorodihydrofluorescein diacetate probe measured intracellular reactive oxygen species content. Western blotting detected the expression of glycolysis- and ferroptosis-related proteins. CCK-8 and EdU staining assays assessed cell proliferation. In the current study, ENO1 was highly expressed in CRC cells. Knockdown of ENO1 markedly reduced the glycolysis and accelerated the ferroptosis in CRC cells. Moreover, the inhibitory effects of WZB117, a specific inhibitor of glycolysis-related glucose transporter type 1, on CRC cell proliferation were further enhanced by ENO1 interference. In addition, silencing of ENO1 inactivated the AKT/STAT3 signaling. The AKT activator SC79 partially reversed the effects of ENO1 deficiency on the AKT/STAT3 signaling, glycolysis, proliferation as well as ferroptosis in CRC cells. In summary, inactivation of AKT/STAT3 signaling mediated by ENO1 inhibition might boost the ferroptosis and suppress the glycolysis in CRC cells.

Ultrasmall metal alloy nanozymes mimicking neutrophil enzymatic cascades for tumor catalytic therapy.

Developing strategies that emulate the killing mechanism of neutrophils, which involves the enzymatic cascade of superoxide dismutase (SOD) and myeloperoxidase (MPO), shows potential as a viable approach for cancer therapy. Nonetheless, utilizing natural enzymes as therapeutics is hindered by various challenges. While nanozymes have emerged for cancer treatment, developing SOD-MPO cascade in one nanozyme remains a challenge. Here, we develop nanozymes possessing both SOD- and MPO-like activities through alloying Au and Pd, which exhibits the highest cascade activity when the ratio of Au and Pd is 1:3, attributing to the high d-band center and adsorption energy for superoxide anions, as determined through theoretical calculations. The Au1Pd3 alloy nanozymes exhibit excellent tumor therapeutic performance and safety in female tumor-bearing mice, with safety attributed to their tumor-specific killing ability and renal clearance ability caused by ultrasmall size. Together, this work develops ultrasmall AuPd alloy nanozymes that mimic neutrophil enzymatic cascades for catalytic treatment of tumors.

RRP12 suppresses cell migration and invasion in colorectal cancer cell via regulation of epithelial-mesenchymal transition.

Background: The survival of patients with advanced colorectal cancer (CRC) is variable. The high rates of recurrence, metastasis, and drug resistance make clinical treatment difficult, which needs to further develop therapeutic and prognostic targets. Ribosomal RNA processing 12 homolog (RRP12), as a nucleolar protein involved in ribosome subunit maturation and export, plays important roles in cell cycle-related processes and the response to DNA damage, and regulates the occurrence and development of various cancers. The primary aim of this study was to identify the function of RRP12 in the process of epithelial-mesenchymal transition (EMT) in CRC. Methods: In this study, the expression of RRP12 in tissue samples and the association with clinicopathological features in CRC was evaluated, and the correlation between RRP12 expression and aggressiveness of CRC was detected. After knockdown of RRP12 gene, the relationship between RRP12 and EMT-related indicators was verified in vivo and in vitro of CRC cells. Identification of RRP12-related genes and pathways through bioinformatic-based analyses was performed to find its potential mechanism. Results: RRP12 is highly expressed in CRC cell lines and clinical samples and is associated with poor survival in CRC patients. RRP12 expression was positively associated with lymph node metastasis, tumor-node-metastasis (TNM) stage, and poor differentiation. Knockdown of RRP12 was found to suppress migration and invasion of CRC cells. RRP12 contributed to the EMT process of CRC cell lines in a ZEB1-mediated manner. RRP12 knockdown was found to reverse metastasis of CRC cells in vivo. Bioinformatic-based analyses indicated that RRP12 could serve as a potential biomarker for prognostic assessment of CRC patients. Conclusions: RRP12 is involved in the tumorigenesis and metastasis of CRC by regulating the EMT process through ZEB1. Thus, RRP12 could be a potential therapeutic target for CRC therapy.

Effect of Megestrol Acetate Combined With Oral Nutrition Supplement in Malnourished Lung Cancer Patients: A Single-Center Prospective Cohort Study.

Background: The optimal treatment of cancer-related malnutrition remains unknown. A single-center prospective cohort study was performed to compare the efficacy of megestrol acetate (MA) combined with oral nutrition supplement (ONS) and MA alone for the treatment of lung cancer-related malnutrition. Methods: 76 eligible patients were prospectively enrolled in two arms, Arm 1 patients (n = 40, 52.6%) received MA 160 mg/d, and Arm 2 patients (n = 36, 47.4%) received MA 160 mg/d combined with ONS 55.8 g/t.i.d, all orally. All patients received anticancer therapy. Treatment duration was 3 months. The primary endpoints were improvements in body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) score. Secondary endpoints were assessed by appetite, mid-upper arm circumference (MAC), serum pre-albumin levels, and serum albumin levels. Results: Baseline levels were comparable between Arm 1 and Arm 2 patients. Compared with Arm 1, primary endpoints (BMI, P = 0.018; ECOG, P = 0.022) and secondary endpoints (MAC, P = 0.025; serum pre-albumin, P = 0.043; and serum albumin, P = 0.034) were improved significantly after treatment in Arm 2. While toxicity was negligible and comparable between Arm 1 and Arm 2. Conclusion: MA combined with ONS may be an effective and safe treatment option for lung cancer-related malnutrition patients. Clinical Trial Registration:www.clinicaltrials.gov, identifier ChiCTR2100049007.