Chitosan‐Gelatin‐EGCG Nanoparticle‐Meditated LncRNA TMEM44‐AS1 Silencing to Activate the P53 Signaling Pathway for the Synergistic Reversal of 5‐FU Resistance in Gastric Cancer. Issue 22 (19th June 2022)

• Record Type: Journal Article
• Authors: Zhou, Mi; Dong, Jiaqi; Huang, Junqing; Ye, Wen; Zheng, Zhousan; Huang, Kangbo; Pan, Yihui; Cen, Junjie; Liang, Yanping; Shu, Guannan; Ye, Sheng; Lu, Xuanxuan; Zhang, Jiaxing
• Is Part Of: Advanced science. Volume 9:Issue 22(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-19
• Subjects: 5‐FU resistance -- gastric cancer -- lncRNAs -- nanoparticles -- p53 signaling pathway; Science -- Periodicals; 505
• DOI: 10.1002/advs.202105077
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: Chemoresistance is one of the leading causes of therapeutic failure in gastric cancer (GC) treatment. Recent studies have shown lncRNAs play pivotal roles in regulating GC chemoresistance. Nanocarriers delivery of small interfering RNAs (siRNAs) to silence cancer‐related genes has become a novel approach to cancer treatment research. However, finding target genes and developing nanosystems capable of selectively delivering siRNAs for disease treatment remains a challenge. In this study, a novel lncRNA TMEM44‐AS1 that is related to 5‐FU resistance is identified. TMEM44‐AS1 has the ability to bind to and sponge miR‐2355‐5p, resulting in the upregulated PPP1R13L expression and P53 pathway inhibition. Next, a new nanocarrier called chitosan‐gelatin‐EGCG (CGE) is developed, which has a higher gene silencing efficiency than lipo2000, to aid in the delivery of a si‐TMEM44‐AS1 can efficiently silence TMEM44‐AS1 expression to synergistically reverse 5‐FU resistance in GC, leading to a markedly enhanced 5‐FU therapeutic effect in a xenograft mouse model of GC. These findings indicate that TMEM44‐AS1 may estimate 5‐FU therapy outcome among GC cases, and that systemic si‐TMEM44‐AS1 delivery combined with 5‐FU therapy is significant in the treatment of patients with recurrent GC. Abstract : 5‐FU resistance is a severe clinical challenge in gastric cancer treatment. In an in vivo 5‐FU‐resistant gastric cancer model, TMEM44‐AS1 is identified as a key factor in inducing 5‐FU resistance by promoting proliferation and inhibiting apoptosis. In addition, novel chitosan‐gelatin‐EGCG nanoparticles are developed to deliver si‐TMEM44‐AS1 into an in vivo xenograft model and succeed reversing 5‐FU resistance.