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Updated: Jun 23, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Circ6834 suppresses non-small cell lung cancer progression by destabilizing ANHAK and regulating miR-873-5p/TXNIP
Maoye Wang1, Xiaoge Ding1, Xinjian Fang2
1Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
Background:
Circular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear.
Methods:
In this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally, the molecular mechanism of circ6834 was revealed by tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter gene assays and rescue experiments.
Results:
Our results showed that circ6834 was downregulated in NSCLC tumor tissues and cell lines. Circ6834 overexpression inhibited NSCLC cell growth and metastasis both in vitro and in vivo, while circ6834 knockdown had the opposite effect. We found that TGF-β treatment decreased circ6834 expression, which was associated with the QKI reduction in NSCLC cells and circ6834 antagonized TGF-β-induced EMT and metastasis in NSCLC cells. Mechanistically, circ6834 bound to AHNAK protein, a key regulator of TGF-β/Smad signaling, and inhibited its stability by enhancing TRIM25-mediated ubiquitination and degradation. In addition, circ6834 acted as a miRNA sponge for miR-873-5p and upregulated TXNIP gene expression, which together inactivated the TGF-β/Smad signaling pathway in NSCLC cells.
Conclusion:
In conclusion, circ6834 is a tumor-suppressive circRNA that inhibits NSCLC progression by forming a negative regulatory feedback loop with the TGF-β/Smad signaling pathway and represents a novel therapeutic target for NSCLC.
Insights
A novel circular RNA, circ6834, is downregulated in non-small cell lung cancer (NSCLC). Overexpression of circ6834 suppresses NSCLC progression by inhibiting the TGF-β/Smad signaling pathway, offering a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in cancer progression and metastasis.
- The specific roles of circRNAs in non-small cell lung cancer (NSCLC) are not fully understood.
Purpose of the Study:
- To identify and characterize novel circRNAs in NSCLC.
- To investigate the biological functions and molecular mechanisms of circ6834 in NSCLC progression.
Main Methods:
- RNA sequencing (RNA-seq) to identify circRNAs.
- In vitro and in vivo experiments to assess circ6834 function.
- Tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter assays, and rescue experiments to elucidate molecular mechanisms.
Main Results:
- hsa_circ_0006834 (circ6834) was identified and found to be downregulated in NSCLC tissues and cell lines.
- Circ6834 overexpression inhibited NSCLC cell growth and metastasis; knockdown promoted these processes.
- Circ6834 antagonized TGF-β-induced epithelial-mesenchymal transition (EMT) and metastasis by interacting with AHNAK and sponging miR-873-5p, thereby inactivating the TGF-β/Smad signaling pathway.
Conclusions:
- Circ6834 acts as a tumor suppressor in NSCLC.
- Circ6834 inhibits NSCLC progression via a negative feedback loop with the TGF-β/Smad signaling pathway.
- Circ6834 represents a potential therapeutic target for NSCLC.
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