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MicroRNA-330-3p functions as an oncogene in human esophageal cancer by targeting programmed cell death 4

Hui Meng1, Kai Wang1, Xuedan Chen1

  • 1Department of Medical Genetics, College of Basic Medicine, Third Military Medical University Chongqing 400038, People's Republic of China.

American Journal of Cancer Research
|June 6, 2015
PubMed

Insights

MicroRNAs regulate gene expression, and abnormal levels are linked to cancer. This study identified miR-330-3p as highly expressed in esophageal squamous cell carcinoma, promoting tumor growth by suppressing PDCD4.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression post-transcriptionally.
  • Aberrant miRNA expression is implicated in the development of various human cancers.
  • Esophageal squamous cell carcinoma (ESCC) is a significant global health concern with complex molecular underpinnings.

Purpose of the Study:

  • To identify novel microRNAs involved in esophageal squamous cell carcinoma (ESCC) carcinogenesis.
  • To elucidate the functional role and molecular mechanism of identified miRNAs in ESCC.
  • To investigate the relationship between specific miRNAs and their target genes in ESCC development.

Main Methods:

  • MicroRNA microarray analysis to screen for differentially expressed miRNAs in ESCC tissues.
  • Quantitative reverse transcription polymerase chain reaction (qRT-PCR) for validation of miRNA expression.
  • In vitro cell assays (proliferation, survival, migration, invasion) and in vivo tumor formation studies in nude mice.
  • Luciferase reporter assay to confirm direct interaction between miRNA and target mRNA.
  • Western blot analysis to assess protein expression levels.

Main Results:

  • miR-330-3p was found to be significantly upregulated in ESCC tumor tissues and cell lines.
  • Overexpression of miR-330-3p promoted ESCC cell proliferation, survival, migration, and invasion, and enhanced tumor formation in vivo.
  • Knockdown of miR-330-3p exhibited opposite effects, inhibiting ESCC progression.
  • miR-330-3p directly targets the 3' untranslated region (UTR) of PDCD4 mRNA.
  • PDCD4 expression was inversely correlated with miR-330-3p levels in ESCC tissues.
  • Silencing PDCD4 mimicked the oncogenic effects of miR-330-3p, promoting cell growth and invasion while inhibiting apoptosis.

Conclusions:

  • miR-330-3p acts as an oncogenic microRNA in esophageal squamous cell carcinoma.
  • The oncogenic role of miR-330-3p in ESCC is, at least partially, mediated through the suppression of its target gene, PDCD4.
  • Targeting miR-330-3p or restoring PDCD4 expression may represent potential therapeutic strategies for ESCC.
Keywords:
Esophageal squamous cell carcinomaPDCD4cell invasioncell proliferationmiR-330-3p

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