Hypoxia-induced MiR-675-5p supports β-catenin nuclear localization by regulating GSK3-β activity in colorectal cancer cell lines

Laura Saieva, Maria Magdalena Barreca, Chiara Zichittella, Maria Giulia Prado, Marco Tripodi, Riccardo Alessandro, Alice Conigliaro

Research output: Contribution to journalArticlepeer-review


The reduction of oxygen partial pressure in growing tumors triggers numerous survival strategies driven by the transcription factor complex HIF1 (Hypoxia Inducible Factor-1). Recent evidence revealed that HIF1 promotes rapid and effective phenotypic changes through the induction of non-coding RNAs, whose contribution has not yet been fully described. Here we investigated the role of the hypoxia-induced, long non-coding RNA H19 (lncH19) and its intragenic miRNA (miR-675-5p) into HIF1-Wnt crosstalk. During hypoxic stimulation, colorectal cancer cell lines up-regulated the levels of both the lncH19 and its intragenic miR-675-5p. Loss of expression experiments revealed that miR-675-5p inhibition, in hypoxic cells, hampered β-catenin nuclear localization and its transcriptional activity, while lncH19 silencing did not induce the same effects. Interestingly, our data revealed that miRNA inhibition in hypoxic cells restored the activity of Glycogen Synthase Kinase 3β (GSK-3β) reducing the amount of P-Ser9 kinase, thus unveiling a role of the miR-675-5p in controlling GSK-3β activity. Bioinformatics analyses highlighted the serine/threonine-protein phosphatases PPP2CA, responsible for GSK-3β activation, among the miR-675-5p targets, thus indicating the molecular mediator through which miR-675-5p may control β-catenin nuclear localization. In conclusion, here we demonstrated that the inhibition of the hypoxia-induced non-coding RNA miR-675-5p hampered the nuclear localization of β-catenin by regulating GSK-3β activity, thus proposing the miR-675-5p as a new therapeutic target for the treatment of colorectal cancer.

Original languageEnglish
Article number3832
Pages (from-to)1-17
Number of pages17
JournalInternational Journal of Molecular Sciences
Issue number11
Publication statusPublished - Jun 1 2020


  • Colorectal cancer
  • Hypoxia
  • Long non-coding H19
  • MiR-675
  • β-catenin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


Dive into the research topics of 'Hypoxia-induced MiR-675-5p supports β-catenin nuclear localization by regulating GSK3-β activity in colorectal cancer cell lines'. Together they form a unique fingerprint.

Cite this