HOXC11 functions as a novel oncogene in human colon adenocarcinoma and kidney renal clear cell carcinoma

Life Sci. 2020 Feb 15:243:117230. doi: 10.1016/j.lfs.2019.117230. Epub 2020 Jan 7.

Abstract

Aims: Accumulating evidence has confirmed the involvement of the homeobox (HOX) gene family in carcinogenesis. HOXC11, belongs to the homeobox-C (HOXC) gene cluster, has been reported to play important roles in the development of several cancers. However, its expression and clinical value in pan-cancer remain elusive.

Materials and methods: Bioinformatics analysis, CCK-8 assay, Flow cytometry and Western blot were used to analyze gene expression and patient survival, cell proliferation, cell apoptosis and protein level, respectively.

Key findings: In this study, we comprehensively analyzed the expression profile and prognostic value of HOXC11 in human pan-cancer using online The Cancer Genome Atlas (TCGA) databases. HOXC11 was widely up-regulated in tumor tissues when compared with the normal tissues in pan-cancer across nine cancer types. In addition, high mRNA level of HOXC11 predicted poor overall survival (OS) of patients with adrenocortical carcinoma (ACC), colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), mesothelioma (MESO) and pancreatic adenocarcinoma (PAAD), respectively. By comparative analysis, we found that HOXC11 was up-regulated and closely correlated patient OS in COAD and KIRC. Functionally, down-regulation of HOXC11 inhibited cell proliferation but promoted apoptosis of COAD and KIRC in vitro. Mechanistically, HOXC11 promoted cell proliferation of COAD and KIRC might by inactivating the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway.

Significance: Our findings suggest that HOXC11 may act as a tumor driving gene in COAD and KIRC.

Keywords: Homeobox-C 11; PPARγ; Pan-cancer; Prognosis; The Cancer Genome Atlas.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Down-Regulation / physiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Oncogenes*
  • PPAR gamma / metabolism
  • Survival Analysis

Substances

  • HOXC11 protein, human
  • Homeodomain Proteins
  • PPAR gamma