Jul 2026· Combinatorial chemistry & high throughput screening· 0 citations
Medicine
TL;DR
The ZNF582-AS1/miR-21-5p/miR-516a-3p/CREBRF regulatory axis provides mechanistic insights into EC tumorigenesis and emphasizes the tumor suppressive effect of ZNF582-AS1.
Abstract
INTRODUCTION
Endometrial Carcinoma (EC) is a prevalent gynecological malignant tumor with a rising incidence rate. Long non-coding RNAs (lncRNAs) are key regulatory factors in tumorigenesis. Although ZNF582-AS1 is an lncRNA that has been linked to other cancers, its role and mechanism in EC have not yet been explored.
Methods
ZNF582-AS1 expression was examined in the GEPIA database and confirmed in 45 pairs of EC/normal tissues and cell lines. Functional assays (including MTT and flow cytometry) were performed after ZNF582-AS1 overexpression. Potential miRNA targets were predicted using bioinformatics and validated using luciferase reporter and RNA Immunoprecipitation (RIP) detection. Downstream targets of miRNA were identified and detected using qPCR and Western blotting. Rescue experiments were conducted to confirm the functional interactions. A xenograft mouse model was used for in vivo validation.
Results
ZNF582-AS1 exhibits marked downregulation in EC tissues and cell lines. Low ZNF582-AS1 expression is linked to unfavorable prognosis. ZNF582-AS1 overexpression suppresses EC cell proliferation, triggers cell cycle arrest, and decreases miR-21-5p and miR-516a3p mRNA levels. Additionally, miR-21-5p/miR-516a-3p suppresses CREBRF expression by binding directly to the 3'-UTR of CREBRF, and ZNF582-AS1 overexpression attenuates this CREBRF suppression. In the in vivo studies, ZNF582-AS1 overexpression effectively inhibited tumor growth in nude mice.
Discussion
These findings support a competitive endogenous RNA mechanism, in which ZNF582-AS1 acts as a molecular sponge for miR-21-5p and miR-516a-3p, thereby alleviating their inhibitory effect on CREBRF expression. The recovery of CREBRF subsequently inhibits EC cell proliferation and promotes G0/G1 phase arrest, possibly by downregulating the CDK4/Cyclin D1 signaling pathway. The in vivo anti-tumor effect of ZNF582-AS1 further supports its biological relevance in EC progression. Overall, the ZNF582-AS1/miR-21-5p/miR516a-3p/CREBRF regulatory axis provides mechanistic insights into EC tumorigenesis and emphasizes the tumor suppressive effect of ZNF582-AS1.
Conclusion
LncRNA ZNF582-AS1 inhibits cell proliferation in EC by regulating the miR-21- 5p/miR-516a-3p/CREBRF axis. ZNF582-AS1 represents a potential treatment target and prognostic marker for EC.
Results highlight lncRNA ABCA9-AS1 as a novel and promising prognostic biomarker that promotes gastric cancer progression by acting as a ceRNA to modulate the miR-497-5p/KIF23 axis.
Yiwen Wu, Yiniu Xia, Hanyu Liu et al.· Current Cancer Drug Targets· 0 citations
The objective of this research is to determine the relative abundances and clinical significance of the long non-coding RNA (lncRNA) RASAL2-AS1 in cervical cancer. Additionally, this study aims to elucidate its molecular mechanism in influencing malignant progression through the regulation of the microRNA-590-5p (miR-590-5p)/PDCD5 axis and the Wnt/β-catenin signaling pathway.
Gene expression of RASAL2-AS1 was assessed in cervical cancer tissues (
n
= 103) using quantitative real-time PCR (qRT-PCR). The impacts on cellular events, epithelial-mesenchymal transition (EMT), and key signaling pathways were evaluated using CCK-8, Transwell, and Western Blot techniques. The target relationships among RASAL2-AS1, miR-590-5p, and PDCD5 were verified via luciferase reporter assays.
RASAL2-AS1 exhibited significantly reduced expression in cervical cancer. Its downregulation was markedly associated with advanced FIGO staging (
P
= 0.014), lymph node metastasis (
P
= 0.035), and poor prognosis, establishing it as an independent indicator of unfavorable outcomes for cervical cancer patients (HR = 0.201, 95% CI = 0.087–0.464,
P
< 0.001). Functionally, the upregulation of RASAL2-AS1 inhibited cervical cancer cell growth and EMT. Mechanistically, RASAL2-AS1 acted as a molecular sponge to sequester miR-590-5p, thereby alleviating its inhibitory effect on PDCD5. Furthermore, RASAL2-AS1 obstructs the Wnt/β-catenin pathway through the miR-590-5p/PDCD5 axis.
RASAL2-AS1 exerts a tumor-suppressive effect in cervical cancer by functioning as a competing endogenous RNA (ceRNA) that modulates the miR-590-5p/PDCD5 axis and regulates the Wnt/β-catenin pathway.
Ke Yin, Yi Li, Mengying Tang· Hereditas· 0 citations
It is indicated that SLC12A9-AS1 is abnormally overexpressed in CRC cells and that its knockdown attenuates malignant phenotypes, at least in part through regulation of miR-139-3p.
Shiyu Zhao, Shuai Zhang, Qiongfeng Tan et al.· Journal of Visualized Experi...· 0 citations
OBJECTIVE
This study aimed to investigate the molecular mechanisms by which AFAP1-AS1 promotes proliferation in oral squamous cell carcinoma (OSCC).
MATERIALS AND METHODS
AFAP1-AS1 expression was examined in OSCC tissues and cell lines. Functional analyses were performed by silencing AFAP1-AS1 in vitro and assessing the resulting changes in CCNA2 expression. Bioinformatic analyses were used to predict microRNAs (miRNAs) potentially interacting with both AFAP1-AS1 and CCNA2, and these interactions were validated using dual-luciferase reporter assays and RNA immunoprecipitation (RIP). Chromatin immunoprecipitation (ChIP) assays were conducted to determine whether c-Myc directly binds to the AFAP1-AS1 promoter, thereby regulating its transcription.
RESULTS
AFAP1-AS1 was significantly upregulated in OSCC tissues and cell lines compared with normal controls. Silencing AFAP1-AS1 led to decreased CCNA2 expression. Both computational predictions and experimental validations indicated that miR-655-3p interacts with AFAP1-AS1 and CCNA2, potentially acting as a regulatory intermediary. ChIP assays further showed that c-Myc directly binds to the promoter region of AFAP1-AS1, suggesting a role in its transcriptional activation.
CONCLUSION
These findings suggest that c-Myc-regulated AFAP1-AS1 may contribute to OSCC proliferation through modulation of the miR-655-3p/CCNA2 axis and provide insight into the molecular mechanisms underlying OSCC progression.
Panpan Liu, Qian Wu, Tao Li· Oral Diseases· 0 citations
Findings indicate that RP3-340N1.2 is aberrantly expressed in LUAD and may participate in tumor-associated cellular behaviors through a miR-4650-5p/SHC1-related regulatory mechanism.
Fang Chen, Yan Yan, Wenting Yang et al.· PLoS ONE· 0 citations
Long non-coding RNAs (lncRNAs) function as pivotal regulators in gastric cancer (GC) pathogenesis via competitive endogenous RNA (ceRNA) networks. However, the precise role of GUSBP11 in GC progression remains inadequately characterized.
This investigation aimed to delineate the biological function of GUSBP11 in GC and to ascertain whether it regulates malignant phenotypes via miR-29c-3p.
GUSBP11, miR-29c-3p, and THBS2 expression levels were quantified in tissues and cells using RT-qPCR. Prognostic value of GUSBP11 in GC was assessed via Kaplan-Meier curve and Cox analysis. In vitro, AGS and HGC-27 cell lines were employed for loss- and gain-function assays. Cellular viability was measured via CCK-8, while migration and invasion capacities were examined using Transwell chambers. Epithelial-mesenchymal transition (EMT) markers were detected by RT-qPCR. Mechanistic interplay was validated through dual-luciferase reporter assays and miRNA inhibitor rescue experiments.
GUSBP11 exhibited upregulation in GC tissues and cell lines, correlating significantly with lower 5-year overall survival. Functional assays demonstrated that GUSBP11 overexpression enhanced viability, migration, and invasion, whereas its knockdown elicited the opposite phenotype. Mechanistically, GUSBP11 operated as a ceRNA by sponging miR-29c-3p, thereby relieving suppression of downstream effector THBS2. Co-transfection with a miR-29c-3p inhibitor effectively reversed the tumor-suppressive consequences of GUSBP11 silencing, restoring THBS2 expression and EMT programming.
The GUSBP11/miR-29c-3p axis exerts a pro-oncogenic influence on GC progression. This regulation offer fresh insights into GC pathophysiology and identifies prospective biomarkers for therapeutic intervention.
