Omslagsbillede

NF–κB mediates transactivation of HNRNPD, resulting in PTEN destabilization and constitutive activation of the PI3K–AKT pathway in oral cancer cells

Guardado en:
Udgivet i:bioRxiv (Jan 5, 2025)
Hovedforfatter: Kumar, Vikas
Andre forfattere: Mittal, Anjani, Kumar, Anurag, Moien Rasheed Lone, Yadav, Vandana, Verma, Priya, Pradhan, Dibyabhaba, Mishra, Deepika, Thakar, Alok, Chauhan, Shaym S
Udgivet:
Cold Spring Harbor Laboratory Press
Fag:
Transcriptomes
PTEN protein
3' Untranslated regions
Autophagy
Oral cancer
TOR protein
Oral squamous cell carcinoma
RNA-binding protein
Therapeutic targets
Cell proliferation
Oral carcinoma
1-Phosphatidylinositol 3-kinase
Cell migration
AKT protein
Senescence
Cell survival
Cell activation
Online adgang:Citation/Abstract
Full Text - PDF
Full text outside of ProQuest
Tags: Tilføj Tag
Ingen Tags, Vær først til at tagge denne postø!
Resumen:Heterogeneous Ribonucleoprotein D (hnRNPD), an RNA binding protein transcriptionally upregulated by NF–κB transcription factor, is associated with poor outcome of Oral Squamous Cell Carcinoma (OSCC). However, the role of hnRNPD in OSCC remains elusive. This study reveals that hnRNPD positively affects the proliferation, migration, invasion, and survival of OSCC cells. Transcriptome profiling in hnRNPD knockout cells identified significant upregulation of PTEN and inhibition of the PI3K/AKT/mTOR axis. HnRNPD mediates the destabilization of PTEN mRNA by binding to the class II AU–Rich Element (ARE) in 3′UTR of PTEN. The expression of hnRNPD and PTEN are strongly negatively correlated in OSCC tissue specimens, further corroborating hnRNPD–mediated PTEN destabilization. The hnRNPD knockout inhibited autophagy, evident by an accumulation of autophagic vesicles and decreased autophagic flux. Mechanistically, the hnRNPD knockout reduced the expression of NF–κB, eventually downregulating its transcriptional target LC3b, a key mediator of autophagy. SA–β–Galactosidase staining in hnRNPD KO cells conclusively demonstrated the onset of cellular senescence. The present study demonstrates hnRNPD driven positive modulation of autophagy via NF–κB, independent of the PI3K/AKT/mTOR axis, highlighting it as a novel therapeutic target for treating oral cancer.Competing Interest StatementThe authors have declared no competing interest.
ISSN:2692-8205
DOI:10.1101/2025.01.05.631360
Fuente:Biological Science Database