MicroRNA‑21 regulates the biological behavior of esophageal squamous cell carcinoma by targeting RASA1

Xiaohua Chen1, Sina Cai2, Baoxia Li3

  • 1Department of Oncology, Panyu Central Hospital, Cancer Institute of Panyu, Guangzhou, Guangdong 511400, P.R. China.

Oncology Reports
|December 21, 2018
PubMed

Insights

MicroRNA-21 (miR-21) promotes esophageal squamous cell carcinoma (ESCC) progression by targeting RASA1. Inhibiting miR-21 demonstrated an antitumor effect, suggesting its therapeutic potential for ESCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-21 (miR-21) is implicated in cancer progression, but its specific role in esophageal squamous cell carcinoma (ESCC) remains unclear.
  • Esophageal squamous cell carcinoma (ESCC) is a significant global health concern requiring novel therapeutic targets.

Purpose of the Study:

  • To elucidate the function of miR-21 in ESCC.
  • To investigate the molecular mechanism underlying miR-21's role in ESCC, focusing on its interaction with RASA1.
  • To evaluate the therapeutic potential of targeting miR-21 in ESCC.

Main Methods:

  • Bioinformatic analysis of GSE13937 dataset to identify differentially expressed miRNAs.
  • Luciferase reporter assay to confirm the direct interaction between miR-21 and RASA1.
  • Quantitative polymerase chain reaction (q-PCR) to assess gene and miRNA expression levels.
  • In vitro cell assays (Transwell) to evaluate proliferation, migration, and invasion.
  • In vivo tumor xenograft model to assess the effect of miR-21 inhibition on tumor growth.

Main Results:

  • miR-21 was significantly upregulated, while its target gene RASA1 was downregulated in ESCC tissues.
  • miR-21 directly targets RASA1, and their expression levels are inversely correlated.
  • Overexpression of miR-21 promoted ESCC cell proliferation, migration, and invasion, partly through regulating Snail and vimentin.
  • Inhibition of miR-21 (using an antagomir) suppressed tumor growth in vivo.

Conclusions:

  • miR-21 promotes ESCC progression by directly targeting RASA1, influencing cell proliferation, migration, invasion, and tumor growth.
  • The miR-21/RASA1 axis, potentially involving Snail and vimentin, represents a key regulatory pathway in ESCC.
  • Inhibition of miR-21 exhibits significant antitumor effects, positioning miR-21 as a promising therapeutic target for ESCC.

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