Abstract
BackgroundAccumulating evidence demonstrates the essential role of long non-coding RNA (lncRNA) in various types of cancers, including pancreatic cancer. However, the functions and regulation mechanism of lncRNA PMSB8-AS1 in pancreatic cancer are largely unclear.MethodsQuantitative reverse transcription PCR (qRT-PCR) is used to examine the expression of PMSB8-AS1 in PC tissues and PC cell lines. The effect of PMSB8-AS1 on the proliferation of PC cells was detected using CCK8 assay, colony assay, and flow cytometry. The effect of PMSB8-AS1 on the migration and invasion of pancreatic cancer cells was detected using a wound-healing assay and transwell migration assay. Bioinformatic analysis, double luciferase reporting assay, western blot, and rescue experiments were used to detect the regulatory relationship between PMSB8-AS1, miR-382–3p, STAT1, and PD-L1.ResultsPMSB8-AS1 expression was upregulated in PC tissues and cell lines and positively associated with the worst survival in patients with PC. The in vitro and in vivo assays demonstrated that overexpression of PMSB8-AS1 significantly promoted pancreatic cancer cell proliferation, migration, and invasion, whereas knockdown of PMSB8-AS1 suppressed cell proliferation, migration, invasion, and EMT, and decreased apoptosis of PC cells. Besides, PMSB8-AS1 directly bound to miR-382–3p downregulated its expression. Besides, PMSB8-AS1 reversed the effect of miR-382–3p on the growth and metastasis of PC cells, which might be targeted on STAT1. Furthermore, STAT1 is the transcriptional factor that activates the expression of PD-L1.ConclusionlncRNA PMSB8-AS1 promotes pancreatic cancer progression via STAT1 by sponging miR-382–3p involving regulation PD-L1.
Highlights
Accumulating evidence demonstrates the essential role of long non-coding RNA in various types of cancers, including pancreatic cancer
PMSB8-AS1 expression increases in Pancreatic cancer (PC) tissue and cell lines To explore the potential involvement of long non-coding RNA (lncRNA) in pancreatic cancer, we analyzed the lncRNA expression analysis across the TCGA database
We explored the mechanism by which lncRNA PSMB8-AS1 promotes PC progression; we showed that PSMB8-AS1 acts as a miRNA sponge in PC to inhibit the function of miRNAs
Summary
Accumulating evidence demonstrates the essential role of long non-coding RNA (lncRNA) in various types of cancers, including pancreatic cancer. The functions and regulation mechanism of lncRNA PMSB8AS1 in pancreatic cancer are largely unclear. Long non-coding RNAs (lncRNAs) exert an essential role in the occurrence and progression of tumors [3, 4], mainly in cancer proliferation, metastasis, and other biological functions associated with tumorigenesis [5, 6]. Zhang et al Journal of Experimental & Clinical Cancer Research (2020) 39:179 studies have shown that lncRNA can participate in the regulation of various biological functions of tumors such as epigenetics, post-transcriptional regulation, genomic stability, and ceRNA regulation mechanism [9,10,11]. A previous study showed that lncRNA GLS-AS mediates a feedback loop between Myc and GLS, providing a potential therapeutic target for metabolic reprogramming in pancreatic cancer. The function and molecular mechanism of lncRNA PSMB8-AS1 remain unclear
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