LINC01355 suppresses breast cancer growth through FOXO3-mediated transcriptional repression of CCND1

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Bolun Ai1, Xiangyi Kong1, Xiangyu Wang1

  • 1Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Cell Death & Disease
|June 28, 2019
PubMed

Insights

Long non-coding RNA LINC01355 acts as a tumor suppressor in breast cancer by inhibiting cell growth and progression. Its re-expression may offer a new therapeutic strategy against breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The 1p36 chromosomal locus contains known tumor suppressor genes.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
  • The function of lncRNAs at the 1p36 locus in breast cancer remains largely unexplored.

Purpose of the Study:

  • To identify and characterize functional lncRNAs with tumor-suppressive activity in breast cancer.
  • To elucidate the molecular mechanism underlying the function of identified lncRNAs.
  • To evaluate the clinical relevance of these lncRNAs in breast cancer patients.

Main Methods:

  • Small interfering RNA (siRNA) screening to identify growth-inhibitory lncRNAs.
  • Overexpression and knockdown experiments in breast cancer cell lines.
  • Cell cycle analysis, proliferation, colony formation, and tumorigenesis assays.
  • Western blotting, qRT-PCR, and RNA immunoprecipitation (RIP) assays.
  • Analysis of clinical breast cancer specimens.

Main Results:

  • LINC01355 was identified as a downregulated lncRNA in breast cancer cells.
  • Overexpression of LINC01355 inhibited breast cancer cell proliferation, colony formation, and tumorigenesis.
  • LINC01355 induced G0/G1 cell cycle arrest by repressing CCND1 expression.
  • LINC01355 stabilized FOXO3 protein, enhancing FOXO3-mediated transcriptional repression of CCND1.
  • Downregulation of LINC01355 correlated with aggressive breast cancer features and poor prognosis.

Conclusions:

  • LINC01355 functions as a tumor suppressor in breast cancer.
  • The tumor-suppressive role of LINC01355 is mediated through the FOXO3/CCND1 pathway.
  • LINC01355 represents a potential therapeutic target for breast cancer treatment.

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