Background:Emerging evidence indicates that the lncRNA FAM83A-AS1 interacts closely with HIF-1α to modulate malignant biological behaviors and glycolytic metabolism in CRC. The mechanism underlying the effects of artemisinin on colorectal cancer (CRC) was investigated using a network pharmacology approach. Methods:The action network of artemisinin was analyzed using network pharmacology. Stable FAM83A-AS1 and HIF-1α knockout cell models were established using a lentiviral system. The effects of artemisinin on cellular functions, including proliferation, metastasis, cell cycle progression, and glycolysis in CRC cells, were assessed through in vitro assays. The expression of HIF-1α was assessed by immunohistochemistry in tumor tissues from 219 patients with CRC, and its clinical associations were analyzed. Results:Artemisinin was predicted to target 96 proteins associated with CRC, including HIF-1α. Artemisinin inhibited proliferation, migration, and glycolysis, and induced cell cycle arrest in CRC cells. Artemisinin reduced the expression levels of Cyclin D1, CDK4, HIF-1α, PKM2, and N-cadherin. Artemisinin promoted proteasome-mediated degradation of HIF-1α protein. HIF-1α upregulated the expression of FAM83A-AS1, whereas knockdown of FAM83A-AS1 reduced HIF-1α expression levels. The expression level of HIF-1α in tumor tissues was significantly higher than that in adjacent non-tumor tissues. HIF-1α expression was associated with tumor node metastasis (TNM) stage, tumor (T)stage, node (N)stage, carcinoembryonic antigen (CEA) levels, recurrence, metastasis, and prognosis in patients with CRC. Conclusions:Artemisinin promoted proteasome-mediated degradation of HIF-1α protein and inhibited CRC progression, potentially through the FAM83A-AS1/HIF-1α regulatory axis.
Background and Objective:Ménage à trois 1 (MNAT1) is an essential scaffolding subunit of the cyclin-dependent kinase (CDK)-activating kinase (CAK) complex and has been increasingly implicated in cancer pathogenesis. Given the accumulating evidence linking MNAT1 to gastrointestinal (GI) malignancies, this narrative review aims to summarize current knowledge regarding the biological functions, oncogenic roles and therapeutic potential of MNAT1 in GI cancers. Methods:A literature search of the relevant databases (PubMed, Web of Science) was conducted, with a focus on recent and key publications in the English language. The search strategy included terms related to MNAT1, GI cancer, CAK complex and therapeutic targeting. Key Content and Findings:MNAT1 stabilizes the CAK complex and promotes cell-cycle progression by enabling CAK-mediated T-loop phosphorylation of cell-cycle CDKs. In addition, CAK functions as a module of the general transcription factor II H (TFIIH) and supports phosphorylation of RNA polymerase II (Pol II) at active promoters, sustaining oncogenic transcription programs. Therapeutic strategies that target MNAT1/CAK include CDK7 inhibition and CAK complex degradation, both of which can suppress transcriptional output and induce cell-cycle arrest. Combination regimens incorporating MNAT1/CAK targeting have also shown preclinical efficacy. Conclusions:This review summarizes current evidence on MNAT1 across multiple malignancies, with a focus on gastrointestinal cancers. We discuss MNAT1 as a potential biomarker for prognosis and treatment response and highlight opportunities and challenges for therapeutically targeting MNAT1/CAK in gastrointestinal cancer.
Background:Esophageal cancer remains a leading cause of cancer-related mortality worldwide, yet the association between coffee consumption-a ubiquitous dietary exposure-and its risk remains inconclusive. This meta-analysis systematically evaluates the association between coffee consumption and esophageal cancer risk, aiming to quantify the overall effect and explore potential heterogeneity. Methods:A systematic search of PubMed, Cochrane Library, Embase, and Web of Science was conducted up to January 2026 for studies comparing coffee intake between esophageal cancer patients and healthy controls. Two reviewers independently extracted data. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Heterogeneity was assessed using the I2 statistic. Certainty of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results:Across 22 included studies encompassing 1,775,988 participants (7,124 cases), neither cohort nor case-control studies demonstrated a significant association between coffee consumption and esophageal cancer risk. The pooled HR from cohort studies was 0.87 (95% CI: 0.74-1.03; I2=24.2%), while the pooled OR from case-control studies was 1.02 (95% CI: 0.77-1.35; I2=66.7%). Conclusions:This meta-analysis found no statistically significant association between coffee consumption and esophageal cancer risk. The available evidence, of low certainty, does not support coffee as a major risk factor. Exploratory analyses on beverage temperature are inconclusive and require confirmation in prospective studies with standardized exposure assessment. This review was registered in PROSPERO (CRD42024562527).
