Genes & Cancer

Fatty changes associated with N-Nitrosodiethylamine (DEN) induced hepatocellular carcinoma: A role of sonic hedgehog signaling pathway

Anindita Tripathy1, Sudhir Thakurela2,3, Manoj Kumar Sahu4, Kanishka Uthansingh4, Ayaskanta Singh4, Jimmy Narayan4, Amrendra Kumar Ajay5, Vinay Singh1 and Ratna Kumari1

1 Disease Biology Laboratory, KIIT School of Biotechnology, KIIT University, Bhubaneswar, India

2 Broad Institute of MIT and Harvard, Cambridge, MA, USA

3 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA

4 Department of Gastroenterology and Hepatobiliary Sciences, IMS and SUM Hospital, Bhubaneswar, India

5 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA


Ratna Kumari, email:

Keywords: hepatocellular carcinoma, adiposity, SHH-E2F1 pathway, lipogenic molecules, adiponectin

Received: April 08, 2020 Accepted: May 08, 2020 Published: May 16, 2020


Backgrounds and Aims: Hepatocellular Carcinoma (HCC) is the leading cause of cancer-related mortality across the world. Non-viral etiological factors including obesity and metabolic syndrome have now become prevalent cause of hepatocellular carcinoma. Sonic Hedgehog (SHH) pathway is activated in hepatocellular carcinoma but its role in regulation of lipogenic molecules during the hepatocarcinogenesis is not known. The aim of present study is to explore the role of SHH pathway in fatty changes associated with hepatocarcinogenesis at different stages and to further correlate the expression of SHH with lipogenic pathways.

Results: Our results demonstrated significant increase in lipidosis and fibrosis in DEN+CCl4 treated animals. It was simultaneously associated with the enhanced expression level of SHH, E2F1, adiponectin, and lipogenic molecules in DEN+CCl4 treated animals. These results were also corroborated with the similar findings in higher stage patients’ biospecimens.

Methods: N-Nitrosodiethylamine (DEN) and Carbon TetraChloride (CCl4) induced hepatocellular acrcinoma model in male Wistar rats were established to study the expression level of SHH pathway and associated fatty changes during different stages of hepatocarcinogenesis. The expression levels of SHH, E2F1, and lipogenic molecules were checked at different stages of hepatocellular carcinoma. These results were further compared with biospecimens of hepatocellular carcinoma patients of different stages.

Conclusions: Our results revealed an unknown aspect of SHH pathway in hepatocarcinogenesis via its control over lipogenesis. It gives insight into the lipogenic properties of DEN+CCl4 induced rodent hepatocarcinogenesis model and how SHH pathway operate to arbitrate this response.

PII: 203