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HDAC5, negatively regulated by miR-148a-3p, promotes colon cancer cell migration

Chunli OuYang1,2, Guang Shu1,3, Jiaxin Liu1

  • 1Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China.

Cancer Science
|May 16, 2022
PubMed

Insights

Histone deacetylases (HDACs) impact colon cancer metastasis. Inhibiting class IIa HDACs, particularly HDAC5, reduced cancer cell migration and invasion, an effect mitigated by miR-148a-3p.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Histone deacetylases (HDACs) regulate gene expression and are implicated in tumor cell growth.
  • Class IIa HDACs play roles in various cellular processes, including cancer progression.

Purpose of the Study:

  • To investigate the role of class IIa HDACs, specifically HDAC5, in colon adenocarcinoma metastasis.
  • To determine the relationship between HDAC5 expression, miR-148a-3p, and tumor progression.

Main Methods:

  • Utilized the class IIa HDAC inhibitor TMP269 to assess its effect on colon adenocarcinoma cell migration.
  • Employed gene silencing techniques to evaluate the impact of HDAC5 and HDAC7 on cell migration.
  • Analyzed HDAC5 expression in tumor tissues and its correlation with miR-148a-3p and tumor progression markers.
  • Investigated the effects of HDAC5 and miR-148a-3p on cancer cell invasion and migration in vitro.
  • Assessed the role of HDAC5 in tumor growth in vivo using an athymic nude mouse model.

Main Results:

  • TMP269 and silencing of HDAC5 or HDAC7 significantly inhibited colon adenocarcinoma cell migration.
  • HDAC5 was highly expressed in colon tumor tissues and correlated with tumor progression.
  • HDAC5 overexpression enhanced cancer cell invasion and migration in vitro.
  • Overexpression of miR-148a-3p counteracted the pro-migratory effects of HDAC5.
  • HDAC5 promoted tumor implantation in vivo.

Conclusions:

  • HDAC5 overexpression contributes to colon adenocarcinoma progression and metastasis.
  • HDAC5 promotes cancer cell invasion and migration, with its effects being modulated by miR-148a-3p.
  • Targeting HDAC5 may represent a therapeutic strategy for colon adenocarcinoma, potentially in conjunction with miR-148a-3p modulation.
Keywords:
HDAC5colon adenocarcinomainvasionmiR-148a-3pmigration

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