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LONG NON-CODING NPTN-IT1 AS A NEW THERAPEUTIC MODALITY FOR HEPATOCELLULAR CARCINOMA

Eman EL-Ahwany 1, Mohamed Elzallat 1, Marwa Hassan 2, Tarek ABOUSHOUSHA 3, Hoda Abu-Taleb 2, Mona Zoheiry 2

Affiliations

1 Theodor Bilharz Research Institute (TBRI), Giza, Egypt

2 Theodor Bilharz Research Institute, Giza, Egypt

3 Theodor Bilharz Research Institute, Cairo, Egypt

Summary

AI Generated

A mouse study tested intrahepatic lncRNA NPTN-IT1 administration as a potential therapeutic modality for hepatocellular carcinoma induced by N-Nitrosodiethylamine.

In a three-group mouse experiment (n=60), Group 2 received DEN weekly for 16 weeks to induce HCC, while Group 3 additionally received intrahepatic lncRNA NPTN-IT1 once weekly for four weeks starting at week 12.
NPTN-IT1 administration resulted in HCC regression with restoration of normal liver architecture as assessed by pathological examination.
Treatment significantly decreased AFP, VEGF, and TNF-α levels (P<0.001) and significantly down-regulated relative expression of cyclin-D1 and TGF-b1 (P<0.001).
The authors propose that lncRNA NPTN-IT1 can be considered a new therapeutic modality for hepatocellular carcinoma based on these preclinical findings.
This work is relevant to researchers investigating novel molecular therapeutic approaches for hepatocellular carcinoma.

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Abstract

Introduction

Hepatocellular carcinoma (HCC) is still an extremely poor prognostic cancer that remains one of the most common and aggressive human malignancies worldwide. The long noncoding RNAs (lncRNAs) have a wide range of functions, including gene transcription, epigenomic regulation, translation of protein-coding genes, RNA turnover, chromatin organization, and genome defense. LncRNAs provide the basis and justification to further develop applications of lncRNA as disease markers and therapeutic targets. LncRNA NPTN-IT1 plays a decisive role in hypoxia-induced metastasis in HCC, and when NPTN-IT1 is downregulated, patients usually face a poor prognosis.

Aims & Methods

In this study, a new therapeutic modality using lncRNA NPTN-IT1 was designed to control HCC progression. Sixty mice were included and categorized into three groups. The 1^st group acted as a normal control group, whereas the 2^nd group acted as a pathological control group and was injected with N-Nitrosodiethylamine (DEN) weekly for 16 weeks. The 3^rd Group was injected intrahepatically with lncRNA NPTN-IT1 once/week for four weeks starting from the 12^th week after initiating the DEN injection. After 16 weeks, animals were euthanized, and liver specimens and blood samples were collected for pathological and biochemical assessment.

Results

Our results showed that lncRNA NPTN-IT1 administration showed regression of HCC with the restoration of normal architecture. The levels of AFP, VEGF, and TNF-α decreased significantly (P< 0.001), and the Relative expression of cyclin-D1 and TGF-b1 was significantly down-regulated (P< 0.001) after NPTN-IT1 administration.

Conclusion

LncRNA NPTN-IT1 can be considered a new therapeutic modality for Hepatocellular carcinoma.

References

This work was supported by Science and Technology Development Fund (STDF), Project NO: 27787 (Innovation Call 4), Cairo, Egypt.

Conference

UEG Week Copenhagen 2023

Topics

Hepatobiliary

Submission format

Abstract

Session

PP 07 Liver & biliary (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

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TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rahul Ravindran 1, Drishya Iyer 2, Daniel Lee 2, Meghan Blitchington 3, Christopher Huckstep 2, Riley Telkamp 3, Kevin Telfer 2, Lillian O'Neal 3, Rachel Mintz 2, Deanna Davis 2, Kibeom Park 2, Nadav Yayon 1, Shashi Kumar 2, Alexandre Gallerand 2, Ahmed Hedayat 2, Changqing Ma 2, Mark Hoofnagle 2, Raphael Blain 4, Adrien Hallou 4, Young-Kwon Hong 5, Simon Travis 4, Matthias Friedrich 4, Huaibin Ko 6, Ryan C. Ungaro 6, Chao Zhou 2, Jean-Frédéric Colombel 6, Fiona Powrie 4, Mark Coles 4, Christopher Buckley 4, Bernd Zinselmeyer 2, Gwendalyn Randolph 2, Rafael Czepielewski 3

Affiliations

1 University of Cambridge, Cambridge, United Kingdom

2 Washington University in St. Louis, Saint Louis, United States

3 Augusta University, Augusta, United States

4 University of Oxford, Oxford, United Kingdom

5 Harvard Medical School, Boston, United States

6 Icahn School of Medicine at Mount Sinai, New York City, United States