UPF1 Promotes Chemoresistance to Oxaliplatin Through Maintenance of Stemness by Increasing Phosphorylated TOP2A in Colorectal Cancer.

Abstract

Background: UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 on oxaliplatin resistance in colorectal cancer (CRC) remains unknown.Methods: Firstly, we investigated the clinical relevance of UPF1 in CRC patients. Then, we explored the influence of UPF1 on chemoresistance to oxaliplatin in vitro and in vivo. Finally, we disclosed the underlying mechanisms of oxaliplatin resistance induced by UPF1.Results: UPF1 is upregulated in CRC and overexpression of UPF1 more likely results in recurrence in CRC patients and predicts a poorer overall survival (OS). UPF1 maintains stemness in CRC cell lines and promotes chemoresistance to oxaliplatin in CRC. UPF1-induced oxaliplatin resistance can be associated with interaction with TOP2A and increasing phosphorylated TOP2A.Conclusions: UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced the stemness and chemoresistance to oxaliplatin by interaction with TOP2A and increase of phosphorylated TOP2A in CRC, which may provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.

LncRNAs in Immune and Stromal Cells Remodel Phenotype of Cancer Cell and Tumor Microenvironment

“…83 Similar results were reported in other cancers, especially in cancer cell's drug resistance. For example, lncRNA H19, WEE2-AS1 and FAL1 in colorectal cancer, [85][86][87] DNM3OS in esophageal cancer, 88 and MEG3 in small cell lung cancer. 89 It can be seen from the above experiments that lncRNAs can maintain the stromal phenotype of CAFs, and participate in the formation of the feedback loop between fibroblasts and tumor cells in the tumor microenvironment.…”

Sulfane sulfur post-translationally modifies the global regulator AdpA to influence actinorhodin production and morphological differentiation of Streptomyces coelicolor

“…The knockout region was replaced by the apramycin resistance gene. The conjugation transfer was accomplished using the methylation-sensitive strain E. coli ET12567/pUZ8002 (containing the mutant plasmid pJTU-adpA) and S. coelicolor M145 following a previously reported protocol (49). The deletion mutant was verified by resistance screening and colony PCR with primers VeradpA-F/R.…”