Interaction Of c-Jun And HOTAIR- Increased Expression Of p21 Converge In Polyphyllin I-Inhibited Growth Of Human Lung...

Area of Science:

• Molecular biology
• Cancer research
• Pharmacology

Background:

• Lung cancer, particularly non-small cell lung cancer (NSCLC), is a major global health concern.
• Polyphyllin I (PPI), a natural compound from Paris polyphylla, previously showed inhibitory effects on NSCLC growth.
• The precise molecular mechanisms of PPI's anti-lung cancer activity require further elucidation.

Purpose of the Study:

• To investigate the detailed molecular mechanisms underlying the anti-lung cancer effects of Polyphyllin I (PPI).
• To explore the roles of HOTAIR, c-Jun, and p21 in PPI's anti-NSCLC activity.

Main Methods:

• Cell proliferation assays (MTT, EdU, colony formation) were employed to assess NSCLC cell growth.
• Western blot and qRT-PCR were used to analyze protein and long non-coding RNA (HOTAIR) expression levels.
• Luciferase reporter assays, gene silencing, and overexpression studies, along with *in vivo* xenograft models, were conducted to validate findings.

Main Results:

• PPI significantly suppressed NSCLC cell proliferation.
• PPI reduced HOTAIR expression while increasing c-Jun and p21 protein levels and p21 promoter activity.
• The interplay between HOTAIR, c-Jun, and p21 was crucial for PPI's anti-proliferative effects, confirmed in both *in vitro* and *in vivo* models.

Conclusions:

• PPI inhibits NSCLC growth via a regulatory axis involving HOTAIR, c-Jun, and p21.
• This pathway converges to induce p21 expression, contributing to the overall anti-cancer effect of PPI.
• The study uncovers a novel molecular mechanism for the anti-lung cancer properties of Polyphyllin I.