The long non-coding RNA LINC00707 interacts with Smad proteins to regulate TGFβ signaling and cancer cell invasion - Centre Eugène Marquis Access content directly
Journal Articles Cell Communication and Signaling Year : 2023

The long non-coding RNA LINC00707 interacts with Smad proteins to regulate TGFβ signaling and cancer cell invasion

Irene Golan
  • Function : Author
Eric Ahlstrom
  • Function : Author
Adam Ameur
Laia Caja
  • Function : Correspondent author
Aristidis Moustakas
  • Function : Correspondent author
  • PersonId : 1058215

Connectez-vous pour contacter l'auteur

Abstract

Background: Long non-coding RNAs (lncRNAs) regulate cellular processes by interacting with RNAs or proteins. Transforming growth factor β (TGFβ) signaling via Smad proteins regulates gene networks that control diverse biological processes, including cancer cell migration. LncRNAs have emerged as TGFβ targets, yet, their mechanism of action and biological role in cancer remain poorly understood. Methods: Whole-genome transcriptomics identified lncRNA genes regulated by TGFβ. Protein kinase inhibitors and RNA-silencing, in combination with cDNA cloning, provided loss- and gain-of-function analyses. Cancer cell-based assays coupled to RNA-immunoprecipitation, chromatin isolation by RNA purification and protein screening sought mechanistic evidence. Functional validation of TGFβ-regulated lncRNAs was based on new transcriptomics and by combining RNAscope with immunohistochemical analysis in tumor tissue. Results: Transcriptomics of TGFβ signaling responses revealed down-regulation of the predominantly cytoplasmic long intergenic non-protein coding RNA 707 (LINC00707). Expression of LINC00707 required Smad and mitogen-activated protein kinase inputs. By limiting the binding of Krüppel-like factor 6 to the LINC00707 promoter, TGFβ led to LINC00707 repression. Functionally, LINC00707 suppressed cancer cell invasion, as well as key fibrogenic and pro-mesenchymal responses to TGFβ, as also attested by RNA-sequencing analysis. LINC00707 also suppressed Smad-dependent signaling. Mechanistically, LINC00707 interacted with and retained Smad proteins in the cytoplasm. Upon TGFβ stimulation, LINC00707 dissociated from the Smad complex, which allowed Smad accumulation in the nucleus. In vivo, LINC00707 expression was negatively correlated with Smad2 activation in tumor tissues. Conclusions: LINC00707 interacts with Smad proteins and limits the output of TGFβ signaling, which decreases LINC00707 expression, thus favoring cancer cell invasion. Video Abstract.
Fichier principal
Vignette du fichier
s12964-023-01273-3 (10.9 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

hal-04279031 , version 1 (10-11-2023)

Licence

Attribution

Identifiers

Cite

Caroline Gelabert, Panagiotis Papoutsoglou, Irene Golan, Eric Ahlstrom, Adam Ameur, et al.. The long non-coding RNA LINC00707 interacts with Smad proteins to regulate TGFβ signaling and cancer cell invasion. Cell Communication and Signaling, 2023, 21 (1), pp.271. ⟨10.1186/s12964-023-01273-3⟩. ⟨hal-04279031⟩
21 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More