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Updated: Dec 31, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
NORAD accelerates chemo-resistance of non-small-cell lung cancer via targeting at miR-129-1-3p/SOX4 axis
Qiang Huang1, Shijiang Xing2, Aiping Peng3
1Department of Pharmacy, Affiliated Xiaolan Hospital of Southern Medical University, Zhongshan, China.
Abstract:
Substantial researches indicated that long non-coding RNAs (lncRNAs) exerted profound effects on chemo-resistance in cancer treatment. Nonetheless, the role of NORAD in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we chose NSCLC cell lines H446 and A549 to explore the function of non-coding RNA activated damage (NORAD) in response to cisplatin (DDP) resistance of NSCLC. Experimental data manifested that NORAD was up-regulated in DDP-resistant NSCLC tissues and cells. NSCLC patients with high NORAD expression suffered a poor prognosis. NORAD knockdown resensitized H446/DDP and A549/DDP to DDP. Besides, NORAD acted as a molecular sponge of miR-129-1-3p. MiR-129-1-3p showed a low level of expression in DDP-resistant NSCLC tissues. Moreover, miR-129-1-3p overexpression impaired DDP resistance in H446/DDP and A549/DDP cells. SOX4 was the downstream target of miR-129-1-3p. Especially, SOX4 overexpression offset the effects of NORAD silence on H446/DDP and A549/DDP cells resistance to DDP. NORAD knockdown resensitized H446/DDP and A549/DDP to DDP in NSCLC via targeting miR-129-1-3p/SOX4 axis, offering a brand-new target for NSCLC chemo-resistance.
Insights
The long non-coding RNA NORAD is upregulated in non-small cell lung cancer (NSCLC) and promotes cisplatin resistance. Targeting NORAD may restore sensitivity to chemotherapy in NSCLC patients.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are implicated in cancer chemo-resistance.
- The specific role of NORAD in non-small cell lung cancer (NSCLC) chemo-resistance is not well understood.
Purpose of the Study:
- To investigate the function of NORAD in cisplatin (DDP) resistance in NSCLC.
- To elucidate the underlying molecular mechanism of NORAD's action in NSCLC chemo-resistance.
Main Methods:
- Utilized NSCLC cell lines (H446 and A549) with induced DDP resistance.
- Assessed NORAD expression in DDP-resistant vs. sensitive NSCLC tissues and cells.
- Performed NORAD knockdown and miR-129-1-3p overexpression experiments.
- Investigated the interaction between NORAD, miR-129-1-3p, and its target SOX4.
Main Results:
- NORAD expression was significantly higher in DDP-resistant NSCLC tissues and cells.
- High NORAD expression correlated with poor prognosis in NSCLC patients.
- NORAD knockdown resensitized NSCLC cells to DDP.
- NORAD sponged miR-129-1-3p, which was downregulated in DDP-resistant cells.
- Overexpression of miR-129-1-3p reduced DDP resistance.
- SOX4 was identified as a downstream target of miR-129-1-3p, and its overexpression reversed the effect of NORAD knockdown.
Conclusions:
- NORAD promotes DDP resistance in NSCLC by sponging miR-129-1-3p and upregulating SOX4.
- The NORAD/miR-129-1-3p/SOX4 axis represents a potential therapeutic target for overcoming chemo-resistance in NSCLC.
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