Abnormal expression of HADH, an enzyme of fatty acid oxidation, affects tumor development and prognosis (Review)

Mol Med Rep. 2022 Dec;26(6):355. doi: 10.3892/mmr.2022.12871. Epub 2022 Oct 14.

Abstract

Tumor occurrence and progression are closely associated with abnormal energy metabolism and energy metabolism associated with glucose, proteins and lipids. The reprogramming of energy metabolism is one of the hallmarks of cancer. As a form of energy metabolism, fatty acid metabolism includes fatty acid uptake, de novo synthesis and β‑oxidation. In recent years, the role of abnormal fatty acid β‑oxidation in tumors has gradually been recognized. Mitochondrial trifunctional protein (MTP) serves an important role in fatty acid β‑oxidation and HADH (two subtypes: α subunit, HADHA and β subunit, HADHB) are important subunits of MTP. HADH participates in the steps of 2, 3 and 4 fatty acid β‑oxidation. However, there is no review summarizing the specific role of HADH in tumors. Therefore, the present study focused on HADH as the main indicator to explore the changes in fatty acid β‑oxidation in several types of tumors. The present review summarized the changes in HADH in 11 organs (cerebrum, oral cavity, esophagus, liver, pancreas, stomach, colorectum, lymph, lung, breast, kidney), the effect of up‑ and downregulation and the relationship of HADH with prognosis. In summary, HADH can be either a suppressor or a promoter depending on where the tumor is located, which is closely associated with prognostic assessment. HADHA and HADHB have similar prognostic roles in known and comparable tumors.

Keywords: HADHA; HADHB; cancer; fatty acid metabolism; fatty acid β‑oxidation.

Publication types

  • Review

MeSH terms

  • Fatty Acids / metabolism
  • Glucose
  • Humans
  • Mitochondrial Trifunctional Protein
  • Mitochondrial Trifunctional Protein, beta Subunit*
  • Neoplasms* / genetics

Substances

  • Fatty Acids
  • Glucose
  • Mitochondrial Trifunctional Protein
  • Mitochondrial Trifunctional Protein, beta Subunit
  • HSD17B10 protein, human

Grants and funding

The present review was supported by grants from Jinan Science and Technology Bureau (grant no. 202019134) and the Shandong Provincial Natural Science Foundation (grant nos. ZR2017MH091, ZR2020QH263 and ZR2021QH142).