LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis

Abstract

Background: Accumulating 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. Methods: Quantitative 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. Results: PMSB8-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. Conclusion: lncRNA PMSB8-AS1 promotes pancreatic cancer progression via STAT1 by sponging miR-382-3p involving regulation PD-L1.

TRAIL Promotes Epithelial-to-mesenchymal Transition by Inducing PD-L1 Expression in Esophageal Squamous Cell Carcinomas

“…In recent years, immune checkpoint inhibitors have also been reported to be associated with EMT, especially PD-L1. Using pancreatic cancer samples, it was reported that PD-L1 promotes EMT and carcinogenesis [15]. Additionally, the role of PD-L1 in regulating EMT has also been reported in lung cancer [14,43] and esophageal cancer [13].…”

“…Recently, the correlation between PD-L1 expression and EMT has attracted increasing attention [12]. It has been demonstrated that PD-L1 promotes EMT in esophageal cancer, pancreatic cancer, breast cancer, and non-small cell lung cancers, leading to tumor progression [13][14][15][16]. Meanwhile, it has been reported that TRAIL and PD-L1 can be expressed simultaneously on tumor cells [17].…”

Novel LncRNA OXCT1-AS1 indicates poor prognosis and contributes to tumorigenesis by regulating miR-195/CDC25A axis in glioblastoma

“…In recent studies, deregulation of lncRNAs was revealed in various malignancies and implicated potential biomarkers and therapeutic targets [ 29 – 31 ]. For example, lncRNA LINC00899 suppresses breast cancer progression by inhibiting miR-425 [ 32 ], lncRNA ZFAS1 regulates oesophageal squamous cell carcinoma cell malignant behaviours via the miR-124/STAT3 axis [ 33 ] and lncRNA MALAT1 promotes GBM proliferation and progression by targeting the miR-199a/ZHX1 axis [ 34 ]. These studies indicated that lncRNAs play an important role in diagnosing and treating human cancers.…”

Using lncRNA Sequencing to Reveal a Putative lncRNA-mRNA Correlation Network and the Potential Role of PCBP1-AS1 in the Pathogenesis of Cervical Cancer

“…Thus far, a series of studies have indicated that lncRNAs exert substantial effects on the pathogenesis of carcinomas, suggesting that lncRNAs might act as prognostic indicators in tumorigenesis and cancer development ( 14 – 16 ). For example, PSMB8-AS1 contributes to pancreatic cancer progression by modulating the miR-382-3p/STAT1/PD-L1 axis ( 21 ). However, limited research has been performed on the transcriptomic profiles of cervical cancer, and the functional roles of lncRNAs in cervical cancer pathogenesis remain largely unknown.…”