Helicase-like Transcription Factor (Hltf) Gene-deletion Promotes Oxidative Phosphorylation (OXPHOS) in Colorectal Tumors of AOM/DSS-treated Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2019 Aug 29

PMID 31461471

Citations 6

Authors

Rebecca A Helmer

Gurvinder Kaur

Lisa A Smith

Beverly S Chilton

Affiliations

Soon will be listed here.

Abstract

The helicase-like transcription factor (HLTF) gene-a tumor suppressor in human colorectal cancer (CRC)-is regulated by alternative splicing and promoter hypermethylation. In this study, we used the AOM/DSS-induced mouse model to show Hltf-deletion caused poor survival concomitant with increased tumor multiplicity, and dramatically shifted the topographic distribution of lesions into the rectum. Differential isoform expression analysis revealed both the truncated isoform that lacks a DNA-repair domain and the full length isoform capable of DNA damage repair are present during adenocarcinoma formation in controls. iPathwayGuide identified 51 dynamically regulated genes of 10,967 total genes with measured expression. Oxidative Phosphorylation (Kegg: 00190), the top biological pathway perturbed by Hltf-deletion, resulted from increased transcription of Atp5e, Cox7c, Uqcr11, Ndufa4 and Ndufb6 genes, concomitant with increased endogenous levels of ATP (p = 0.0062). Upregulation of gene expression, as validated with qRT-PCR, accompanied a stable mtDNA/nDNA ratio. This is the first study to show Hltf-deletion in an inflammation-associated CRC model elevates mitochondrial bioenergetics.

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