TL;DR
Higher circ_0027446 expression was associated with larger tumor size, lymph node metastasis, advanced TNM stage, and shorter overall survival, and may contribute to tumor progression and immune escape-related changes, at least partly through the miR-6882-3p/HOXB9 axis.
BACKGROUND AND STUDY AIMS Circular RNAs (circRNAs) are characterized by their covalently closed-loop configuration. They are increasingly being recognized as key modulators of tumorigenesis and cancer progression. Studies have revealed aberrant hsa_circ_0001839 expression in various cancer types. However, its effect and underlying mechanisms in gastric cancer (GC) remain unknown. Therefore, we systematically investigated the clinical importance of hsa_circ_0001839 in gastric cancer and its molecular mechanisms in disease progression. PATIENTS AND METHODS Paired tumor specimens and histologically normal adjacent tissues were collected from 117 patients with GC who underwent curative surgery. RT-qPCR was performed to measure hsa_circ_0001839 expression in clinical samples and cell lines. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate the prognostic relevance of this circRNA. Lastly, cell transfection, CCK-8, Transwell invasion, and dual-luciferase reporter assays were performed to validate the functional effects on GC cells and regulatory interactions with target genes. RESULTS Compared with matched non-tumor tissues, hsa_circ_0001839 expression was markedly increased in gastric cancer tissues. High hsa_circ_0001839 expression significantly correlated with larger tumor dimensions, deeper invasion depth, advanced TNM stage, and the presence of lymph node metastasis. Multivariate Cox analysis revealed that high hsa_circ_0001839 expression is an independent predictor of poor prognosis. Functionally, hsa_circ_0001839 knockdown effectively suppressed the malignant phenotypes of GC cells, significantly decreasing their proliferative, migratory, and invasive abilities. Mechanistically, hsa_circ_0001839 directly binds to the 3'-untranslated region of miR-634, thereby repressing its function. CONCLUSION As an oncogenic circRNA, hsa_circ_0001839 is critically implicated in gastric cancer progression and unfavorable patient outcomes, underscoring its dual application as a promising prognostic biomarker and a potential therapeutic intervention target.
Laryngeal squamous cell carcinoma (LSCC), the most common subtype of laryngeal cancer, often exhibits poor responsiveness to conventional therapies. Although circRNAs have been implicated in various malignancies, their roles in LSCC remain incompletely understood. This study aimed to investigate the function and underlying mechanism of circ_0075961 in LSCC progression. Expression levels of circ_0075961 and ZEB1 were measured in 32 paired LSCC and ANT tissues using RT-qPCR. Functional assays, including CCK-8, colony formation, and transwell assays, were conducted to assess cell proliferation, migration, and invasion. The interaction between circ_0075961 and ZEB1 was validated by RIP assay. EMT-related protein expression was evaluated by WB. Additionally, a xenograft mouse model was used to verify the role of ZEB1 in vivo. The results showed that circ_0075961 and ZEB1 were significantly upregulated in LSCC tissues and cell lines. Knockdown of circ_0075961 or ZEB1 significantly inhibited the proliferation, migration, and invasion of LSCC cells. Mechanistically, circ_0075961 appeared to regulate these phenotypes by modulating the EMT process through ZEB1. Knockdown of circ_0075961 led to increased E-cadherin and decreased ZEB1, N-cadherin, and Vimentin expression. In vivo, ZEB1 knockdown markedly suppressed tumor growth in a xenograft model. In conclusion, circ_0075961 is associated with malignant phenotypes in LSCC, including tumor cell proliferation, migration, invasion, and EMT, with these effects potentially linked to ZEB1 regulation. These findings suggest that circ_0075961 may serve as a potential therapeutic target and a promising candidate for further exploration as a biomarker, providing new insights into LSCC treatment strategies.
Lung adenocarcinoma (LUAD), the most common subtype of lung cancer, is associated with substantial global mortality. Nuclear receptor coactivator 5 (NCOA5) has been implicated in several malignancies; however, its functional role and regulatory mechanisms in LUAD remain largely unknown. In this study, NCOA5 expression was evaluated in 94 paired LUAD and adjacent tissues using immunohistochemistry, RT-PCR, and Western blotting. Functional analyses were conducted using shRNA knockdown, CRISPR-mediated knockout, and overexpression models to assess the effects of NCOA5 on LUAD cell proliferation, migration, invasion, apoptosis, cell cycle progression, and organoid formation. Xenograft models were used to validate tumorigenicity in vivo. IP-MS and co-immunoprecipitation identified NCOA5-interacting proteins, while ChIP-seq and dual-luciferase assays interrogated downstream transcriptional regulation. NCOA5 was significantly upregulated in LUAD tissues and associated with advanced stage, poor differentiation, and reduced overall survival, serving as an independent prognostic factor ( P < .040). NCOA5 knockdown inhibited LUAD cell proliferation, migration, invasion, induced G0/G1 arrest, promoted apoptosis, reduced organoid formation, and suppressed xenograft growth, whereas NCOA5 overexpression produced the opposite effects. Among 39 candidate interacting proteins identified by IP-MS, ZCCHC3 was validated as a direct NCOA5-binding partner. ZCCHC3 depletion phenocopied NCOA5 loss and reversed NCOA5-induced proliferation, migration, invasion, and colony formation, supporting a functional NCOA5–ZCCHC3 interaction. ChIP-seq analysis identified fibroblast growth factor 22 (FGF22) as a direct transcriptional target of NCOA5. FGF22 was markedly downregulated in LUAD tissues and higher FGF22 expression was associated with improved patient survival. NCOA5 suppressed FGF22 transcription, while NCOA5 inhibition increased FGF22 expression. Functionally, FGF22 knockdown enhanced LUAD aggressiveness, whereas FGF22 restoration abrogated the oncogenic effects of NCOA5 in vitro and in vivo. Collectively, these findings identify a previously unrecognized NCOA5–ZCCHC3/FGF22 axis that drives LUAD progression and provide new mechanistic insight into the role of NCOA5 in LUAD biology.
Cervical cancer is a leading cause of female malignancy worldwide. While microRNA-4327 (miR-4327) has been implicated as a potential oncogene, its functional role and molecular mechanisms in cervical cancer pathogenesis remain unclear. This study aimed to determine the oncogenic function of miR-4327 and elucidate its downstream regulatory mechanism in cervical cancer pathogenesis. We measured miR-4327 expression in clinical cervical cancer tissues and cell lines using quantitative real-time PCR (qRT-PCR). We then assessed its effects on proliferation, migration, invasion, and cell cycle progression through functional assays including cell counting kit-8 (CCK-8), colony formation, transwell, and flow cytometry. To evaluate tumor growth in vivo, we established a xenograft model in non-obese diabetic (NOD)-severe combined immune-deficient (scid) mice. Using bioinformatic analysis and luciferase reporter assays, we identified TP53 as a direct target of miR-4327 and further validated this regulatory relationship with gain- and loss-of-function experiments. We found that miR-4327 was significantly upregulated in cervical cancer and promoted malignant phenotypes such as proliferation, migration, invasion, and cell cycle progression in vitro. Consistent with this, overexpression of miR-4327 accelerated tumor growth in vivo. Mechanistically, we confirmed TP53 as a direct functional target of miR-4327. Knocking down TP53 phenocopied the oncogenic effects of miR-4327, while restoring TP53 expression rescued the tumor-promoting effects mediated by miR-4327. These findings reveal a novel miR-4327/TP53 regulatory axis and nominate miR-4327 as a potential therapeutic target for intervention.