Hu, J.; Li, H.; Mao, N.; Di, H.; Zhao, Y.; Chen, J.; Wang, A. Lipidomic Analysis on Gender-Dependent Hepatocellular Carcinogenesis in Hras12V Transgenic Mice. Preprints2023, 2023111406. https://doi.org/10.20944/preprints202311.1406.v1
APA Style
Hu, J., Li, H., Mao, N., Di, H., Zhao, Y., Chen, J., & Wang, A. (2023). Lipidomic Analysis on Gender-Dependent Hepatocellular Carcinogenesis in Hras12V Transgenic Mice. Preprints. https://doi.org/10.20944/preprints202311.1406.v1
Chicago/Turabian Style
Hu, J., Jun Chen and Aiguo Wang. 2023 "Lipidomic Analysis on Gender-Dependent Hepatocellular Carcinogenesis in Hras12V Transgenic Mice" Preprints. https://doi.org/10.20944/preprints202311.1406.v1
Abstract
Lipid dysregulation is critically involved in hepatocellular carcinoma (HCC). Further, male predi-lection and Ras pathway hyperactivation are distinct characteristics of HCC. However, mecha-nisms underlying their connections remain unknown. The aim of the present study was to perform a comprehensive lipidomics analysis of a Hras12V transgenic mice (Ras-Tg) model of HCC induced by hepatocyte-specific Ras pathway activation and characterized by male predilection and a dis-rupted lipid metabolism. A total of 3437 lipids were identified in HCC (T) and peri-tumor tissues (P) of Ras-Tg mice and liver tissues of wild-type mice (W) of both sexes. Longitudinal comparisons of W, P, and T yielded 359 differentially expressed lipids (DELs) in male mice and 306 DELs in female mice. Generally, glycerolipid accumulation, glycerophospholipid reduction and monounsaturated fatty acid synthesis improvement were more frequent in T compared to P. The expression change pattern analysis revealed common and characteristic DELs positively/negatively associated with HCC or the Ras oncogene. Further lipid metabolism pathway investigations revealed that disordered lipid and fatty acid biosynthesis contributed to glycerolipid accumulation and glycerophospholipid re-duction in T. Comparisons between P and W suggests that different responses to the Ras oncogene in mice of different sexes, as well as higher amounts of aberrantly regulated lipids in males, may contribute to male-biased hepatocarcinogenesis. However, lateral comparisons between sexes showed a converging trend during hepatocarcinogenesis, explaining the poor efficacy for gen-der-specific therapies. In conclusion, the common and characteristic DELs and lipid metabolism pathways in HCC initiated by the Ras oncogene from sexually dimorphic hepatocytes provide novel insights into the clinical diagnosis and management of HCC.
Keywords
lipidomics; hepatocellular carcinoma; ras oncogene; sex disparity
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
