Abstract
Background: An increasing number of long non-coding RNAs (lncRNAs) is recognized to be associated with drug resistance in CRC.Methods: 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. Results: The lncRNA PGM5-AS1 was identified by analyzing data from the original microarray data set of colon cancer (GSE75970). PGM5-AS1 additionally suppressed acquired oxaliplatin resistance in CRC cells. Malignant phenotype of PGM5-AS1 was inhibited by recruiting SRSF3 to activate alternative splicing and being a sponge specific to hsa-miR-423-5p.Conclusions: Downregulation of PGM5-AS1 in oxaliplatin-resistant colon cancer tissues and cell lines is induced by transcriptional inhibition of GFI1B. PGM5-AS1 recruited SRSF3 to activate alternative splicing to downregulate the expression of PAEP. In addition, PGM5-AS1 could competitively bind with hsa-miR-423-5p to upregulate the expression of NME1. PGM5-AS1 inhibits the proliferation, invasion, migration and acquired oxaliplatin resistance of colon cancer cells through these two pathways.
Modulation of Oncogenic Transcription and Alternative Splicing by β-Catenin and an RNA Aptamer in Colon Cancer Cells
