Oxaliplatin resistance inevitably occurs in almost all cases of metastatic colorectal cancer (CRC), and it is important to study the roles of lncRNAs and their specific regulatory mechanisms in oxaliplatin resistance. Exosomes are increasingly designed for drug or functional nucleic acid delivery due to their properties, thereby improving the effectiveness of cancer therapy. The results of this study show that the low expression of PGM5 antisense RNA 1 (PGM5-AS1) in colon cancer is induced by transcription inhibitor, GFI1B. PGM5-AS1 prevents proliferation, migration, and acquired oxaliplatin tolerance of colon cancer cells. Exosomes encapsulating oxaliplatin and PGM5-AS1 can reverse drug resistance. For identifying differentially expressed target genes regarding PGM5-AS1, RNA transcriptome sequencing was performed. The mechanism by which PGM5-AS1 regulates its target genes was explored by performing experiments such as fluorescent in situ hybridization assay, dual-luciferase reporter gene assay, and RNA immunoprecipitation. The results show that by recruiting SRSF3, PGM5-AS1 activates alternate splicing to downregulate PAEP expression. For hsa-miR-423-5p, PGM5-AS1 can also act as a sponge to upregulate the NME1 expression.

中文翻译：

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工程外泌体共同递送 PGM5-AS1 和奥沙利铂以逆转结肠癌的耐药性

几乎所有转移性结直肠癌（CRC）都不可避免地出现奥沙利铂耐药，研究lncRNAs在奥沙利铂耐药中的作用及其特定调控机制具有重要意义。由于其特性，外泌体越来越多地设计用于药物或功能性核酸递送，从而提高癌症治疗的有效性。本研究结果表明，结肠癌中 PGM5 反义 RNA 1 (PGM5-AS1) 的低表达是由转录抑制剂 GFI1B 诱导的。PGM5-AS1 可防止结肠癌细胞的增殖、迁移和获得性奥沙利铂耐受。包裹奥沙利铂和 PGM5-AS1 的外泌体可以逆转耐药性。为了鉴定关于 PGM5-AS1 的差异表达靶基因，进行了 RNA 转录组测序。原位杂交测定、双荧光素酶报告基因测定和 RNA 免疫沉淀。结果表明，通过招募 SRSF3，PGM5-AS1 激活交替剪接以下调 PAEP 表达。对于 hsa-miR-423-5p，PGM5-AS1 也可以作为海绵上调 NME1 的表达。