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Long noncoding RNA OCC-1 suppresses cell growth through destabilizing HuR protein in colorectal cancer

Yang Lan1, Xuewei Xiao1, Zhengchi He1

  • 1Center for Functional Genomics and Bioinformatics, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, Sichuan, P.R. China.

Nucleic Acids Research
|June 23, 2018
PubMed

Insights

Long noncoding RNA OCC-1 suppresses colorectal cancer (CRC) by targeting HuR. OCC-1 destabilizes HuR, reducing cell growth and regulating cell cycle transitions, revealing its tumor-suppressive role in CRC.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Colorectal cancer (CRC) is a major global health concern.
  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
  • The specific function of overexpressed in colon carcinoma-1 (OCC-1) lncRNA in CRC remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the functional role of OCC-1 in colorectal cancer.
  • To investigate the molecular mechanisms by which OCC-1 influences CRC progression.

Main Methods:

  • RNA interference (RNAi) for OCC-1 knockdown.
  • In vitro and in vivo cell growth assays.
  • Analysis of cell cycle phase transitions.
  • Investigation of protein-protein interactions using ubiquitination assays.
  • Western blotting to assess protein levels.

Main Results:

  • OCC-1 exhibits a tumor-suppressive function in CRC.
  • Knockdown of OCC-1 promotes cell proliferation and inhibits G0/G1 and G1/S phase transitions.
  • Overexpression of OCC-1 suppresses cell growth.
  • OCC-1 binds to and destabilizes HuR (ELAVL1), a cancer-associated RNA binding protein.
  • OCC-1 facilitates HuR ubiquitination and degradation via β-TrCP1, reducing HuR and target mRNA levels.

Conclusions:

  • lncRNA OCC-1 acts as a tumor suppressor in colorectal cancer.
  • OCC-1 regulates cancer cell growth by modulating HuR stability at the post-transcriptional level.
  • This mechanism involves enhancing HuR ubiquitination and degradation, impacting downstream target mRNAs crucial for cell growth.

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