MiR-520a-5p/PPP5C regulation pattern is identified as the key to gemcitabine resistance in pancreatic cancer

Abstract

ObjectiveTo explore the effects of the expression level of miR-520-5p/PPP5C in pancreatic cancer cells and exosomes on cell viability, angiogenesis, autophagy, which involved in the mechanism of gemcitabine resistance in pancreatic cancer.MethodsAPSC-1 cell line was treated with gemcitabine, after which its exosomes were extracted for NTA assay. Subsequently, the drug resistance of APSC-1 cells was assayed using CCK8, as well as the activity of HUVEC cells treated with exosomes from each group of APSC-1 cells after drug resistance treatment as well as overexpression treatment. Five groups of HUVEC cells treated with exosomes were subjected to in vitro tubule formation assay. levels of PPP5C in each group of ASPC-1 cells and their exosomes, levels of overexpressed PPP5C, and related exosomal proteins were examined by WB. mRNA expression levels of PPP5C and levels of miR-520a were examined by qPCR The relationship between miR-520a-5p and PPP5C was investigated. After that, the autophagy of PPP5C was detected. Finally, it was analyzed by TCGA database for survival prognosis analysis.ResultsAPSC-1 cells had an IC50 value of 227.1 μM for gemcitabine, elevated PPP5C expression, drug resistance, and enhanced HUVEC cell activity; exosomes CD9, CD63, and CD81 were significantly expressed in all groups; meanwhile, enhanced PPP5C expression not only promoted in vitro tubule formation but also increased autophagy levels; meanwhile, its relationship with miR-520-5p and There was a targeted inhibitory relationship between its level and miR-520-5p and PPP5C, and its elevated level also led to a decrease in the survival level of patients over 3-5 years.ConclusionPPP5C has a prognostic role in pancreatic cancer by promoting the value-added and invasion of pancreatic cancer cells, and a targeted inhibitory relationship between miR-520-5p and PPP5C was found.

Exosomal HSPB1, interacting with FUS protein, suppresses hypoxia‐induced ferroptosis in pancreatic cancer by stabilizing Nrf2 mRNA and repressing P450

“… 26 Other studies demonstrated that exosomes from gemcitabine‐resistant pancreatic cancer stem cells mediate the horizontal transfer of drug‐resistant traits to gemcitabine‐sensitive pancreatic cancer cells by delivering miR‐210 27 or miR‐520‐5p. 28 In this study, we reported that SW1990 cells‐derived exosomes delivered HSPB1 protein into surrounding cells, and HSPB1 interacted with the RNA binding protein FUS functioning as a proto‐oncogene.…”

“…It was reported that human pancreatic cancer cells SW1990 derived exosomes promoted the proliferation, migration and cell cycle progression of HPDE cells, while exosomes with downregulated expression of hsa_circ_0000069 inhibited HPDE cell proliferation, migration and cell cycle progression by inhibiting STIL expression and inhibited pancreatic cancer progression 26 . Other studies demonstrated that exosomes from gemcitabine‐resistant pancreatic cancer stem cells mediate the horizontal transfer of drug‐resistant traits to gemcitabine‐sensitive pancreatic cancer cells by delivering miR‐210 27 or miR‐520‐5p 28 . In this study, we reported that SW1990 cells‐derived exosomes delivered HSPB1 protein into surrounding cells, and HSPB1 interacted with the RNA binding protein FUS functioning as a proto‐oncogene.…”

CMTM7 inhibits breast cancer progression by regulating Wnt/β-catenin signaling

“…The miR-29b-3p inhibited thyroid cancer invasion and migration by regulating COL1A1 and COL5A1 [ 37 ]. The miR-520a-5p plays an essential role in regulating gemcitabine resistance by directly targeting PPP5C in pancreatic cancer [ 38 ]. Furthermore, a previous study demonstrated the miR-182-5p regulation on CMTM7 in breast cancer, demonstrating that EVs-miR-182-5p promoted tumor progression by regulating the CMTM7/EGFR/AKT signaling axis [ 39 ].…”