NAT1 is a critical prognostic biomarker and inhibits proliferation of colorectal cancer through modulation of PI3K/Akt/mTOR

Future Oncol. 2021 Jul;17(19):2489-2498. doi: 10.2217/fon-2020-0992. Epub 2021 Apr 28.

Abstract

The aim of this study was to analyze the correlations between NAT1 and clinicopathological features of and prognosis in colorectal cancer (CRC). RNA sequencing data and clinical information were retrieved from The Cancer Genome Atlas database. Wilcoxon test, logistic regression and Kaplan-Meier method were used to estimate the association between NAT1 and prognosis in CRC. In vitro experiments were conducted to confirm the role of NAT1. NAT1 is significantly less expressed in CRC and independently associated with poor prognosis in CRC patients. The authors further confirmed that expression of NAT1 was significantly lower in SW116 colon cancer cells than in NCM460 cells. Overexpressed NAT1 obviously inhibited the growth of CRC cells by downregulating phosphorylation of the PI3K/Akt/mTOR signaling pathway. NAT1 may be a potential therapeutic target for CRC.

Keywords: NAT1; Oncomine; PI3K/Akt/mTOR; TCGA; colorectal cancer; prognosis.

Plain language summary

Lay abstract Colorectal cancer (CRC) is a common malignancy worldwide. Because of the limited understanding of the pathogenesis and prognostic factors associated with CRC, the treatment effect in CRC remains poor. In the present study, the authors demonstrate that NAT1 is significantly less expressed in CRC and independently associated with poor prognosis in CRC patients. NAT1 may exert antitumor activity by inhibiting phosphorylation of the PI3K/Akt/mTOR signaling pathway. These results suggest that NAT1 may be a prognostic factor in and therapeutic target for CRC.

MeSH terms

  • Arylamine N-Acetyltransferase / analysis
  • Arylamine N-Acetyltransferase / metabolism*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Datasets as Topic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isoenzymes / analysis
  • Isoenzymes / metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / genetics
  • Prognosis
  • RNA-Seq
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • Isoenzymes
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1
  • MTOR protein, human
  • TOR Serine-Threonine Kinases