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HOPX Is an Epigenetically Inactivated Tumor Suppressor and Overexpression of HOPX Induce Apoptosis and Cell Cycle

Qinghua You1, Yuanyuan Geng1, Huiying Ye1

  • 1Department of Pathology, Shanghai Pudong Hospital, Shanghai 201399, People's Republic of China.

Oncotargets and Therapy
|July 2, 2020
PubMed
Abstract

Insights

Homeobox Homeobox (HOPX) is epigenetically silenced in breast cancer. Restoring HOPX suppresses tumor growth, suggesting its potential as a breast cancer treatment target.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Aberrant DNA methylation is implicated in breast cancer progression by silencing gene expression.
  • The methylation status of HOPX is elevated in breast cancer tissues, but its functional role remains unclear.

Purpose of the Study:

  • To investigate the role of HOPX in breast cancer progression.
  • To explore the potential of HOPX as a therapeutic target for breast cancer.

Main Methods:

  • Bisulfite sequencing and methylation-specific PCR (MSP) to assess HOPX methylation.
  • Cellular assays (flow cytometry, wound healing, Transwell) to evaluate apoptosis, migration, and invasion.
  • Western blot to analyze protein expression (HOPX, p21, cyclin D1, CDK4).

Main Results:

  • HOPX promoter regions (cg218995965, cg24862548) were significantly hypermethylated in breast cancer tissues and cell lines.
  • Overexpression of HOPX inhibited proliferation and induced apoptosis in breast cancer cells.
  • Upregulation of HOPX suppressed migration, invasion, and induced cell cycle arrest via p21, cyclin D1, and CDK4 modulation.
  • HOPX overexpression inhibited tumor growth in vivo.

Conclusions:

  • HOPX functions as a tumor suppressor epigenetically silenced in breast cancer.
  • Restoring HOPX expression can impede breast cancer progression.
  • HOPX represents a potential therapeutic target for breast cancer treatment.
Keywords:
DNA methylationHOPXapoptosisbreast cancer

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