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miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma

Li-Li Mei1, Wen-Jun Wang1, Yun-Tan Qiu1

  • 1Medical School, Kunming University of Science and Technology, Kunming, China.

Plos One
|October 3, 2017
PubMed

Insights

MicroRNA-125b-5p (miR-125b-5p) is downregulated in esophageal squamous cell carcinoma (ESCC). Its reintroduction inhibits cancer cell proliferation, migration, and invasion by targeting HMGA2.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are crucial regulators in human cancer development.
  • miR-125b-5p is reportedly downregulated in esophageal squamous cell carcinoma (ESCC), but its functional roles remain unclear.

Purpose of the Study:

  • To investigate the functional roles and underlying mechanisms of miR-125b-5p loss in ESCC progression.

Main Methods:

  • MicroRNA microarray and Gene Expression Omnibus (GEO) datasets were used to confirm miR-125b-5p downregulation in ESCC.
  • In vitro assays assessed the effects of ectopic miR-125b-5p expression on cell proliferation, migration, invasion, and senescence.
  • Quantitative real-time PCR and Western blotting were employed to analyze gene and protein expression levels of cell cycle regulators, epithelial-mesenchymal transition (EMT) markers, matrix metalloproteinases (MMPs), and the target gene HMGA2.

Main Results:

  • miR-125b-5p was confirmed to be significantly downregulated in ESCC tissues.
  • Overexpression of miR-125b-5p suppressed ESCC cell proliferation, migration, and invasion, while inducing cellular senescence.
  • miR-125b-5p negatively regulated cell cycle genes (CCNA2, CCND1, CCNE1), EMT markers (E-cadherin, N-cadherin, Slug), MMPs (MMP2, MMP7, MMP13), and its direct target gene HMGA2 at both mRNA and protein levels.
  • Knockdown of HMGA2 partially mimicked the effects of miR-125b-5p overexpression on cell cycle and EMT markers.

Conclusions:

  • miR-125b-5p functions as a tumor suppressor in ESCC.
  • Overexpression of miR-125b-5p inhibits ESCC cell proliferation, migration, and invasion, partly through the downregulation of HMGA2.
  • These findings highlight miR-125b-5p as a potential therapeutic target for ESCC treatment.

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