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Published on: May 14, 2016
circUBAP2 exacerbates malignant capabilities of NSCLC by targeting KLF4 through miR-3182 modulation
Guanying Zheng1, Jianyuan Huang2, Wenshu Chen2
1Department of Pulmonary and Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China.
Abstract:
Chemo-resistance and refractoriness remain challenges for Non-small cell lung cancer (NSCLC) patients and the underlying molecular mechanisms haven't been fully explained. In this study, we investigated the influence of circUBAP2 on the NSCLC tumor cells. This study might provide novel therapeutic targets for NSCLC treatment. Clinical samples and NSCLC cell lines were used to investigate circUBAP2 expressions and their impact on tumor cell chemo-resistance. CCK8 and transwell assays were conducted to explore the differences of NSCLC tumor proliferation and migration capabilities affected by circUBAP2. Dual-luciferase reporter gene assay was performed to explore the detailed molecular mechanism of circUBAP2 regulation network. circUBAP2 exhibited significantly elevated average level in our clinical samples of NSCLC, compared with normal tissues. CircUBAP2 level was positively correlated with disease stage and metastatic status. circUBAP2 significantly enhanced the migration, proliferation and chemo-resistance of NSCLC cell lines. Further experiments indicated that circUBAP2 promoted malignant biological behavior of NSCLC tumor cells by targeting KLF4 through modulating miR-3182 expression. Our study demonstrated for the first time that circUBAP2 played an important role exacerbating malignant capabilities of NSCLC. circUBAP2-miR3182-KLF4 regulative network demonstrated in this study could be a novel therapeutic target for future NSCLC treatment.
Insights
Circular RNA UBAP2 (circUBAP2) is elevated in non-small cell lung cancer (NSCLC) and promotes tumor progression and chemo-resistance. Targeting the circUBAP2-miR3182-KLF4 pathway may offer new therapeutic strategies for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chemo-resistance and refractoriness are significant challenges in non-small cell lung cancer (NSCLC) treatment.
- The molecular mechanisms underlying these challenges in NSCLC are not fully elucidated.
- Identifying novel therapeutic targets is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of circular RNA UBAP2 (circUBAP2) in NSCLC progression and chemo-resistance.
- To explore the underlying molecular mechanisms of circUBAP2 action in NSCLC.
- To evaluate circUBAP2 as a potential therapeutic target for NSCLC.
Main Methods:
- Analysis of circUBAP2 expression in clinical NSCLC samples and cell lines.
- CCK8 and transwell assays to assess NSCLC cell proliferation and migration.
- Dual-luciferase reporter gene assay to elucidate the circUBAP2 regulatory network.
Main Results:
- circUBAP2 expression was significantly higher in NSCLC tissues compared to normal tissues.
- Elevated circUBAP2 levels correlated positively with NSCLC disease stage and metastasis.
- circUBAP2 enhanced NSCLC cell migration, proliferation, and chemo-resistance.
- circUBAP2 targets KLF4 by modulating miR-3182 expression, promoting malignant behaviors.
Conclusions:
- circUBAP2 plays a critical role in exacerbating the malignant potential of NSCLC.
- The circUBAP2-miR3182-KLF4 regulatory network represents a novel therapeutic target for NSCLC treatment.
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