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Silencing CDR1as inhibits colorectal cancer progression through regulating microRNA-7

Wentao Tang1, Meiling Ji1, Guodong He1

  • 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Oncotargets and Therapy
|April 25, 2017
PubMed

Insights

Circular RNAs (circRNAs) like CDR1as are implicated in colorectal cancer (CRC) progression. This study shows CDR1as promotes CRC by inhibiting microRNA-7 (miR-7), thereby upregulating EGFR and IGF-1R, leading to poor survival.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their role in regulating gene expression via microRNA (miRNA) interactions.
  • Dysregulation of circRNAs is implicated in various cancers, including colorectal cancer (CRC).

Purpose of the Study:

  • To investigate the expression and function of antisense to CDR1as (CDR1as) in colorectal cancer (CRC).
  • To elucidate the molecular mechanisms underlying CDR1as's role in CRC progression, focusing on its interaction with microRNA-7 (miR-7) and its downstream targets.

Main Methods:

  • Analysis of CDR1as expression in CRC tissues versus normal adjacent mucosa.
  • Assessment of the correlation between CDR1as expression and clinicopathological features (tumor size, T stage, lymph node metastasis, overall survival).
  • In vitro studies involving CDR1as knockdown and miR-7 overexpression/inhibition in CRC cells to evaluate effects on proliferation and invasion.
  • Mechanistic investigations into the regulation of Epidermal Growth Factor Receptor (EGFR) and Insulin-like Growth Factor 1 Receptor (IGF-1R) by CDR1as and miR-7.

Main Results:

  • CDR1as expression was significantly higher in CRC tissues and correlated with advanced tumor size, T stage, lymph node metastasis, and poorer overall survival.
  • Downregulation of CDR1as inhibited CRC cell proliferation and invasion while increasing miR-7 expression.
  • Ectopic expression of miR-7 suppressed CRC cell proliferation and invasion, and miR-7 inhibition rescued the effects of CDR1as knockdown.
  • CDR1as silencing reduced EGFR and IGF-1R expression, an effect partially reversed by miR-7 inhibition.
  • Positive correlations were observed between CDR1as, EGFR, and IGF-1R expression in CRC samples.

Conclusions:

  • Dysregulated CDR1as expression plays a significant role in CRC progression.
  • CDR1as promotes CRC by sponging miR-7, leading to the upregulation of oncogenes EGFR and IGF-1R.
  • CDR1as represents a potential therapeutic target for colorectal cancer.
Keywords:
CDR1ascolorectal cancermicroRNA-7proliferation

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