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Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth

Lu-Lu Wang1, Hui-Hui Guo1, Yun Zhan1

  • 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.

Oncotarget
|April 28, 2017
PubMed

Insights

Small active RNA (saRNA) p21-saRNA-322 boosts p21 gene expression to inhibit colorectal cancer growth. Studies show it induces apoptosis, cell cycle arrest, and reduces tumor growth in vivo.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Therapeutics

Background:

  • Down-regulation of p21 is a hallmark of colorectal cancer.
  • Small active RNA (saRNA) p21-saRNA-322 demonstrates potential for cancer therapy by stimulating p21 gene expression.
  • Colorectal cancer presents a viable target for in situ saRNA delivery.

Purpose of the Study:

  • To investigate the efficacy of p21-saRNA-322 in colorectal cancer models.
  • To evaluate the molecular mechanisms underlying p21-saRNA-322's anti-cancer effects.
  • To assess the in vivo tumor-suppressing capabilities of p21-saRNA-322.

Main Methods:

  • Transfection of human colorectal cancer cell lines (HCT-116, HCT-116 (p53-/-), HT-29) with p21-saRNA-322.
  • Measurement of p21 mRNA and protein expression via RT-PCR and Western blot.
  • In vitro assessment of cellular effects and in vivo evaluation using a xenograft colorectal tumor model in mice.

Main Results:

  • p21-saRNA-322 transfection significantly increased p21 mRNA and protein levels in all tested cell lines.
  • Treatment induced apoptosis, cell cycle arrest at G0/G1, reduced colony formation, and promoted senescence.
  • In vivo studies demonstrated significant inhibition of tumor growth and enhanced p21 activation in a mouse xenograft model.

Conclusions:

  • p21-saRNA-322 effectively up-regulates p21 expression in colorectal cancer cells.
  • The saRNA exhibits potent anti-proliferative and tumor-suppressing effects in vitro and in vivo.
  • p21-saRNA-322 represents a promising therapeutic strategy for colorectal cancer treatment.
Keywords:
colorectal cancerp21-saRNA-322small active RNA (saRNA)tumor growth suppressionxenograft tumor mode

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