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Down-regulation of miR-144 promotes thyroid cancer cell invasion by targeting ZEB1 and ZEB2

Hongyu Guan1, Weiwei Liang, Zhiwei Xie

  • 1Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, Guangdong, China.

Endocrine
|June 28, 2014
PubMed

Insights

MicroRNA-144 (miR-144) is down-regulated in thyroid cancer, suppressing tumor cell invasion and migration. This microRNA acts as a tumor suppressor by targeting ZEB1 and ZEB2, key regulators in thyroid cancer progression.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Thyroid cancer is the most common endocrine malignancy with increasing global incidence.
  • The molecular mechanisms driving thyroid cancer remain incompletely understood.
  • MicroRNAs (miRNAs) are critical regulators of tumorigenesis.

Purpose of the Study:

  • To investigate the role of miR-144 in thyroid cancer.
  • To determine if miR-144 expression is altered in thyroid tumors.
  • To elucidate the functional impact and molecular targets of miR-144 in thyroid cancer cells.

Main Methods:

  • Quantitative analysis of miR-144 expression in thyroid cancer tissues versus normal tissues.
  • In vitro functional assays (invasion and migration) in thyroid cancer cell lines (K1 and WRO) with miR-144 restoration.
  • Luciferase reporter assays to confirm direct binding of miR-144 to the 3'-untranslated regions of ZEB1 and ZEB2.
  • Rescue experiments to assess the effect of ZEB1/ZEB2 restoration on miR-144-mediated inhibition of cell invasion.

Main Results:

  • miR-144 expression was significantly decreased in thyroid cancer tissues compared to normal tissues.
  • Restoring miR-144 in thyroid cancer cells suppressed their invasion and migration capabilities.
  • miR-144 directly targets and suppresses the expression of ZEB1 and ZEB2, known inhibitors of E-cadherin.
  • Overexpression of ZEB1 or ZEB2 partially reversed the inhibitory effects of miR-144 on cell invasion.

Conclusions:

  • miR-144 functions as a tumor suppressor in thyroid cancer.
  • The miR-144/ZEB1/ZEB2 axis plays a significant role in regulating thyroid cancer cell metastasis.
  • Down-regulation of miR-144 may contribute to thyroid cancer progression.

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