1. 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.
- Author
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Zhou M, Dong J, Huang J, Ye W, Zheng Z, Huang K, Pan Y, Cen J, Liang Y, Shu G, Ye S, Lu X, and Zhang J
- Subjects
- Animals, Antimetabolites, Antineoplastic pharmacology, Antimetabolites, Antineoplastic therapeutic use, Catechin analogs & derivatives, Catechin pharmacology, Catechin therapeutic use, Cell Line, Tumor, Chitosan pharmacology, Chitosan therapeutic use, Fluorouracil pharmacology, Fluorouracil therapeutic use, Gelatin pharmacology, Gelatin therapeutic use, Gene Expression Regulation, Neoplastic, Humans, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, MicroRNAs genetics, RNA, Antisense genetics, RNA, Antisense metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Repressor Proteins genetics, Repressor Proteins metabolism, Signal Transduction genetics, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Antineoplastic Agents metabolism, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Drug Resistance, Neoplasm drug effects, Drug Resistance, Neoplasm genetics, Drug Resistance, Neoplasm physiology, Gene Silencing drug effects, Gene Silencing physiology, Nanoparticles therapeutic use, RNA genetics, RNA metabolism, Stomach Neoplasms drug therapy, Stomach Neoplasms genetics, Stomach Neoplasms metabolism
- 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., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)
- Published
- 2022
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