Targeting long non-coding RNA PVT1/TGF-β/Smad by p53 prevents glioma progression

Abstract

Glioma is a primary intracranial malignant tumor with poor prognosis, and its pathogenesis is unclear. This study discussed the impact of p53/lncRNA plasmacytoma variant translocation 1 (lncRNA PVT1)/transforming growth factor beta (TGF-β)/Smad axis on the biological characteristics of glioma. Glioma and normal tissues were collected, in which relative lncRNA PVT1 and p53 expression was assessed. Pearson’s analysis was adopted for the correlation analysis between lncRNA PVT1 and p53. Short interfering RNA (siRNA) against lncRNA PVT1 (siRNA-PVT1), siRNA-p53 or both was transfected into the glioma cells to evaluate effects of lncRNA PVT1 and p53 on cell proliferation, migration, invasion, and apoptosis. Mouse xenograft model of glioma was established to verify function of lncRNA PVT1 and p53 in vivo . Relationship among p53, lncRNA PVT1 and TGF-β/Smad was predicted and confirmed. Glioma tissues and cells showed downregulated p53 expression and increased lncRNA PVT1 expression. An adverse relationship was noted between p53 expression and lncRNA PVT1 expression. p53 was shown to be enriched in the lncRNA PVT1 promoter region and resulted in its suppression. p53 inhibited glioma cell proliferation, migration, and invasion, and induced apoptosis as well as arrested tumor growth by downregulating lncRNA PVT1. LncRNA PVT1was found to bind to TGF-β and activate TGF-β/Smad pathway, promoting progression of glioma. Consequently, p53 exerts anti-oncogenic function on glioma development by suppressing lncRNA PVT1 and subsequently inactivating TGF-β/Smad pathway.

Hydrogel on a Smart Nanomaterial Interface to Carry Therapeutics for Digitalized Glioma Treatment

“…Synthetic cancer-sensing circuits have been designed to recognize cancer cells based on intracellular gene expression profiles [ 8 , 11 ]. PI3K pathway inhibitors loaded with liposomes, cationic liposomes containing the TP53 gene plasmid, siRNAs against EGFR and PDGFRA, siRNAPVT1, siRNAp53, siRNASTAT3, and PDL1 have been investigated for glioma therapy [ 40 , 41 , 42 ]. Multi-colored RNA circuits (generating tumor suppressor microRNAs targeting key glioma driver genes) have been employed in nanohydrogels to produce the circuit’s logical synthetic genetics.…”

IncRNA VIM-AS1 expression is positively correlated with the prognosis and immune infiltration in lung adenocarcinoma

“…p53 inhibits glioma cell proliferation, migration and invasion,which stops tumor growth, and induces apoptosis by downregulating PVT1 expression. PVT1 binds to TGF-β to activate the TGF-β/Smad signaling pathway to promote glioma progression [12] . ITGB1-DT is overexpressed in gastric adenocarcinoma tissues.…”

“…Multiple projects have shown that lncRNAs are associated with the prognosis and the growth of cancer cells [12][13][14][15] . Glioma tissues and cells showed signi cant downregulation of p53 expression and a signi cant increase in lncRNA PVT1 expression.…”

Long non-coding RNA PVT1: A promising chemotherapy and radiotherapy sensitizer

“…In another study, lncPVT1 influence bone morphogenetic protein (BMP) signaling pathway by regulating miR-128-3p/GREM1 axis, thereby promoting glioma cell proliferation, invasion, migration, and antiapoptosis (112). A recent study showed that tumor suppressor gene p53 inhibits glioma cell proliferation, migration, and invasion while inducing apoptosis by blocking lncPVT1/TGFb/Smad signaling pathway (113). Researchers knocked down lncPVT1 expression levels in SHG-44 glioma cells, added different concentrations of paclitaxel, and then measured their apoptosis rate.…”