Co-upregulation of MEG3 and TUG1 lncRNAs by Hyaluronic Acid-based Nanoparticles Confers Selective Toxicity in Lung Adenocarcinoma

Document Type : Research Article

Authors

1 Department of Molecular Cell Biology and Genetics, Bu.C., Islamic Azad University, Bushehr, Iran

2 Department of Biology, Faculty of Sciences, Arak University, Arak, Iran

3 Department of Biology, Ra.C., Islamic Azad University, Rasht, Iran

4 Department of Biology, Bu.C., Islamic Azad University, Bushehr, Iran

Abstract

Lung cancer remains a leading cause of cancer-related mortality globally, underscoring the need for novel targeted therapies. Dysregulation of long non-coding RNAs (lncRNAs), such as the tumor suppressor MEG3 and the context-dependent lncRNA TUG1, plays a critical role in non-small cell lung cancer (NSCLC) pathogenesis and chemoresistance. This study aimed to develop a targeted nanotherapeutic system to modulate these lncRNAs and selectively eliminate cancer cells. Hyaluronic acid (HA) and Gallic acid (GA)-conjugated to Glucose (Glu)-functionalized Fe₃O₄ nanoparticles (Fe₃O₄@Glu-HA-GA NPs) were synthesized and characterized by scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analyses. These nanoparticles target CD44-overexpressing cancer cells via HA functionalization. In vitro studies on A549 (lung adenocarcinoma) and MRC5 (normal lung fibroblast) cells revealed that Fe₃O₄@Glu-HA-GA NPs exhibited potent and selective cytotoxicity, with an IC₅₀ of 70 µg/mL in A549 cells, significantly lower than in MRC5 cells (IC₅₀= 214 µg/mL). qRT-PCR analysis demonstrated a cancer cell-specific transcriptional response, where the treatment significantly upregulated MEG3 by 1.58-fold (p< 0.01) and TUG1 by 1.33-fold (p< 0.01) in A549 cells compared to untreated controls. This selective lncRNA dysregulation correlated with the observed anticancer activity. In conclusion, the Fe₃O₄@Glu-HA-GA nanoplatform represents a promising strategy for targeted lung cancer therapy by selectively perturbing key lncRNA networks, offering a potential avenue to overcome nonspecific toxicity and enhance therapeutic efficacy.

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References

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Journal of Genetic Resources
Volume 12, Issue 1
Issue in Progress
2026
Pages 41-52

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