Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth

Rafael Sebastián Fort, Cecilia Mathó, Murilo Vieira Geraldo, María Carolina Ottati, Alex Shimura Yamashita, Kelly Cristina Saito, Katia Ramos Moreira Leite, Manuel Méndez, Noemí Maedo, Laura Méndez, Beatriz Garat, Edna Teruko Kimura, José Roberto Sotelo-Silveira, María Ana Duhagon

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer. Methods: Nc886 promoter methylation status and its correlation with patient clinical parameters or DNMTs levels were evaluated in TCGA and specific GEO prostate tissue datasets. Nc886 level was measured by RT-qPCR to compare normal/neoplastic prostate cells from radical prostatectomies and cell lines, and to assess nc886 response to demethylating agents. The effect of nc886 recovery in cell proliferation (in vitro and in vivo) and invasion (in vitro) was evaluated using lentiviral transduced DU145 and LNCaP cell lines. The association between the expression of nc886 and selected genes was analyzed in the TCGA-PRAD cohort. Results: Nc886 promoter methylation increases in tumor vs. normal prostate tissue, as well as in metastatic vs. normal prostate tissue. Additionally, nc886 promoter methylation correlates with prostate cancer clinical staging, including biochemical recurrence, Clinical T-value and Gleason score. Nc886 transcript is downregulated in tumor vs. normal tissue -in agreement with its promoter methylation status- and increases upon demethylating treatment. In functional studies, the overexpression of nc886 in the LNCaP and DU145 cell line leads to a decreased in vitro cell proliferation and invasion, as well as a reduced in vivo cell growth in NUDE-mice tumor xenografts. Finally, nc886 expression associates with the prostate cancer cell cycle progression gene signature in TCGA-PRAD. Conclusions: Our data suggest a tumor suppressor role for nc886 in the prostate, whose expression is epigenetically silenced in cancer leading to an increase in cell proliferation and invasion. Nc886 might hold clinical value in prostate cancer due to its association with clinical parameters and with a clinically validated gene signature.

Original languageEnglish (US)
Article number127
JournalBMC cancer
Volume18
Issue number1
DOIs
StatePublished - Feb 2 2018
Externally publishedYes

Keywords

  • Cancer
  • DNA methylation
  • Metastasis
  • MiR-886
  • Nc886
  • Prostate
  • TCGA
  • Tumor suppressor
  • Vault RNA
  • Vtrna2-1

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth'. Together they form a unique fingerprint.

Cite this