LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis
LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis
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DOI：
10.1186/s13046-020-01687-8
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发表时间：
2020-09-05
影响因子：
11.3
通讯作者：
Sun, Chengyi
中科院分区：
文献类型：
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作者：
Zhang, Hao;Zhu, Changhao;Sun, Chengyi
越来越多的证据表明长链非编码RNA（lncRNA）在包括胰腺癌在内的各种癌症中起着重要作用。然而，lncRNA PMSB 8-AS 1在胰腺癌中的功能和调控机制尚不清楚。方法采用定量逆转录聚合酶链反应（qRT-PCR）检测PMSB 8-AS 1在PC组织和PC细胞系中的表达。采用CCK-8法、集落形成法和流式细胞仪检测PMSB 8-AS 1对PC细胞增殖的影响。采用创伤愈合实验和transwell迁移实验检测PMSB 8-AS 1对胰腺癌细胞迁移和侵袭能力的影响。采用生物信息学分析、双荧光素酶报告分析、蛋白质印迹和拯救实验检测PMSB 8-AS 1、miR-382- 3 p、STAT 1和PD-L1之间的调控关系。结果PMSB 8-AS 1在PC组织和细胞系中表达上调，并与PC患者的最差生存率呈正相关。体外和体内实验表明，PMSB 8-AS 1的过表达显著促进胰腺癌细胞的增殖、迁移和侵袭，而PMSB 8-AS 1的敲低抑制细胞增殖、迁移、侵袭和EMT，并减少PC细胞的凋亡。PMSB 8-AS 1与miR-382- 3 p直接结合后，其表达下调。PMSB 8-AS 1逆转了miR-382- 3 p对PC细胞生长和转移的影响，其作用机制可能与STAT 1有关。此外，STAT 1是激活PD-L1表达的转录因子。结论lncRNA PMSB 8-AS 1通过STAT 1介导miR-382- 3 p参与PD-L1的调控，促进胰腺癌的进展。
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.