Nanoconjugated long non-coding RNA MEG3 as a new therapeutic approach for Hepatocellular carcinoma

Mohamed Elzallat; Marwa Hassan; Nabila Elkramani; Tarek Aboushousha; Ahmed AbdelLatif; Noha Helal; Hoda Abu-Taleb; Eman El-Ahwany

doi:10.1016/j.heliyon.2023.e15288

Nanoconjugated long non-coding RNA MEG3 as a new therapeutic approach for Hepatocellular carcinoma

Heliyon. 2023 Apr 6;9(4):e15288. doi: 10.1016/j.heliyon.2023.e15288. eCollection 2023 Apr.

Authors

Mohamed Elzallat¹, Marwa Hassan¹, Nabila Elkramani², Tarek Aboushousha³, Ahmed AbdelLatif², Noha Helal³, Hoda Abu-Taleb⁴, Eman El-Ahwany¹

Affiliations

¹ Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt.
² Biotechnology Program and Biology Department, School of Science and Engineering, American University in Cairo, Cairo, Egypt.
³ Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt.
⁴ Enviromental Research Department, Theodor Bilharz Research Institute, Giza, Egypt.

Abstract

Background: Hepatocellular carcinoma (HCC) is an aggressive human cancer with a poor prognosis. Long non-coding RNAs (lncRNA) have multiple functions: epigenomic regulation, gene transcription, protein-coding gene translation, and genome defense. The involvement of lncRNAs in therapy offers a vast step in cancer treatment.

Objective: In the current study, a novel therapeutic regimen using polymer nanoparticle-mediated delivery of lncRNA was designed to control the progression of hepatocarcinogenesis.

Methods: One hundred mice were divided into 5 groups. The first group served as a normal-control group and was injected with saline, whereas the pathological-control group (the second group) was injected with N-Nitrosodiethylamine (DEN) weekly for 16 weeks. Group 3, Group 4, and Group 5 were injected intrahepatically with polymer nanoparticles (NPs) alone, lncRNA MEG3 alone, and conjugated NPs, respectively, once/week for four weeks starting on the 12th week after DEN injection. After 16 weeks, animals were euthanized, and liver specimens and blood samples were collected for pathological, molecular, and biochemical assessment.

Results: Compared to the pathological-control group, nanoconjugates lncRNA MEG3 demonstrated a significant improvement in histopathology and tumour-associated biomarkers. Furthermore, the expression of the SENP1 and PCNA was downregulated.

Conclusion: MEG3 conjugated nanoparticles can be considered a novel therapeutic regimen for HCC.

Keywords: HCC; LncRNAs; MEG3; Polymer nanoparticles; Therapy.