Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2020

Open Access 01-12-2020 | Metastasis | Research

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

Authors: Hao Zhang, Changhao Zhu, Zhiwei He, Shiyu Chen, Lin Li, Chengyi Sun

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2020

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Strobel O, Neoptolemos J, Jager D, Buchler MW. Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol. 2019;16:11–26.CrossRef
2.
Buscail L, Bournet B, Cordelier P. Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2020;17(3):153–68.
3.
Chan JJ, Tay Y. Noncoding RNA:RNA Regulatory Networks in Cancer. Int J Mol Sci. 2018;19(5).
4.
Ren X. Genome-wide analysis reveals the emerging roles of long non-coding RNAs in cancer. Oncol Lett. 2020;19(1):588–94.
5.
Chen L, Zhang J, Chen Q, Ge W, Meng L, Huang X, Shen P, Yuan H, Shi G, Miao Y et al. Long noncoding RNA SOX2OT promotes the proliferation of pancreatic cancer by binding to FUS. Int J Cancer. 2020;147(1):175–88.
6.
Shi L, Hong X, Ba L, He X, Xiong Y, Ding Q, Yang S, Peng G. Long non-coding RNA ZNFX1-AS1 promotes the tumor progression and metastasis of colorectal cancer by acting as a competing endogenous RNA of miR-144 to regulate EZH2 expression. Cell Death Dis. 2019;10:150.CrossRef
7.
Pan S, Shen M, Zhou M, Shi X, He R, Yin T, Wang M, Guo X, Qin R. Long non-coding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924. Cell Death Dis. 2019;10:883.CrossRef
8.
Zhou WY, Zhang MM, Liu C, Kang Y, Wang JO, Yang XH. Long non-coding RNA LINC00473 drives the progression of pancreatic cancer via upregulating programmed death-ligand 1 by sponging microRNA-195–5p. J Cell Physiol. 2019;234:23176–89.CrossRef
9.
Tang XJ, Wang W, Hann SS. Interactions among lncRNAs, miRNAs and mRNA in colorectal cancer. Biochimie. 2019;163:58–72.CrossRef
10.
Arnes L, Liu Z, Wang J, Maurer C, Sagalovskiy I, Sanchez-Martin M, Bommakanti N, Garofalo DC, Balderes DA, Sussel L et al. Comprehensive characterisation of compartment-specific long non-coding RNAs associated with pancreatic ductal adenocarcinoma. Gut. 2019;68(3):499–511.
11.
Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9:703–19.CrossRef
12.
Wang CJ, Zhu CC, Xu J, Wang M, Zhao WY, Liu Q, Zhao G, Zhang ZZ. The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol Cancer. 2019;18:115.CrossRef
13.
Yao N, Fu Y, Chen L, Liu Z, He J, Zhu Y, Xia T, Wang S. Long non-coding RNA NONHSAT101069 promotes epirubicin resistance, migration, and invasion of breast cancer cells through NONHSAT101069/miR-129–5p/Twist1 axis. Oncogene. 2019;38:7216–33.CrossRef
14.
More S, Zhu Z, Lin K, Huang C, Pushparaj S, Liang Y, Sathiaseelan R, Yang X, Liu L. Long non-coding RNA PSMB8-AS1 regulates influenza virus replication. RNA Biol. 2019;16:340–53.CrossRef
15.
Giulietti M, Righetti A, Principato G, Piva F. LncRNA co-expression network analysis reveals novel biomarkers for pancreatic cancer. Carcinogenesis. 2018;39:1016–25.CrossRef
16.
Wang W, Lou W, Ding B, Yang B, Lu H, Kong Q, Fan W. A novel mRNA-miRNA-lncRNA competing endogenous RNA triple sub-network associated with prognosis of pancreatic cancer. Aging (Albany NY). 2019;11:2610–27.CrossRef
17.
Ling J, Wang F, Liu C, Dong X, Xue Y, Jia X, Song W, Li Q. FOXO1-regulated lncRNA LINC01197 inhibits pancreatic adenocarcinoma cell proliferation by restraining Wnt/beta-catenin signaling. J Exp Clin Cancer Res. 2019;38:179.CrossRef
18.
Lei S, He Z, Chen T, Guo X, Zeng Z, Shen Y, Jiang J. Long non-coding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway. J Exp Clin Cancer Res. 2019;38:470.CrossRef
19.
Shi J, Zhang Y, Qin B, Wang Y, Zhu X. Long non-coding RNA LINC00174 promotes glycolysis and tumor progression by regulating miR-152–3p/SLC2A1 axis in glioma. J Exp Clin Cancer Res. 2019;38:395.CrossRef
20.
Liu L, Wang HJ, Meng T, Lei C, Yang XH, Wang QS, Jin B, Zhu JF. lncRNA GAS5 inhibits cell migration and invasion and promotes autophagy by targeting miR-222–3p via the GAS5/PTEN-signaling pathway in CRC. Mol Ther Nucleic Acids. 2019;17:644–56.CrossRef
21.
Shen G, Mao Y, Su Z, Du J, Yu Y, Xu F. PSMB8-AS1 activated by ELK1 promotes cell proliferation in glioma via regulating miR-574–5p/RAB10. Biomed Pharmacother. 2020;122:109658.CrossRef
22.
Wang Y, Chen W, Lian J, Zhang H, Yu B, Zhang M, Wei F, Wu J, Jiang J, Jia Y, et al. The lncRNA PVT1 regulates nasopharyngeal carcinoma cell proliferation via activating the KAT2A acetyltransferase and stabilizing HIF-1alpha. Cell Death Differ. 2020;27:695–710.CrossRef
23.
Guo T, Gong C, Wu P, Battaglia-Hsu SF, Feng J, Liu P, Wang H, Guo D, Yao Y, Chen B et al. LINC00662 promotes hepatocellular carcinoma progression via altering genomic methylation profiles. Cell Death Differ. 2020;27(7):2191–205.
24.
Tian X, Wu Y, Yang Y, Wang J, Niu M, Gao S, Qin T, Bao D. Long non-coding RNA LINC00662 promotes M2 macrophage polarization and hepatocellular carcinoma progression via activating Wnt/beta-catenin signaling. Mol Oncol. 2020;14:462–83.CrossRef
25.
Yang L, Dong Y, Li Y, Wang D, Liu S, Wang D, Gao Q, Ji S, Chen X, Lei Q, et al. IL-10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF-kappaB/Notch1 pathway in non-small cell lung cancer. Int J Cancer. 2019;145:1099–110.CrossRef
26.
Liu R, Lu Z, Gu J, Liu J, Huang E, Liu X, Wang L, Yang J, Deng Y, Qian J, et al. MicroRNAs 15A and 16–1 activate signaling pathways that mediate Chemotaxis of immune regulatory B cells to colorectal tumors. Gastroenterology. 2018;154:637–51.CrossRef
27.
Elion DL, Jacobson ME, Hicks DJ, Rahman B, Sanchez V, Gonzales-Ericsson PI, Fedorova O, Pyle AM, Wilson JT, Cook RS. Therapeutically active RIG-I agonist induces immunogenic tumor cell killing in breast cancers. Cancer Res. 2018;78:6183–95.CrossRef
28.
Liu LZ, Zhang Z, Zheng BH, Shi Y, Duan M, Ma LJ, Wang ZC, Dong LQ, Dong PP, Shi JY, et al. CCL15 recruits suppressive monocytes to facilitate immune escape and disease progression in hepatocellular carcinoma. Hepatology. 2019;69:143–59.CrossRef
29.
Zhang Y, Ma CA, Lawrence MG, Break TJ, O'Connell MP, Lyons JJ, Lopez DB, Barber JS, Zhao Y, Barber DL, et al. PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients. J Exp Med. 2017;214:2523–33.CrossRef
30.
Mataki H, Seki N, Mizuno K, Nohata N, Kamikawaji K, Kumamoto T, Koshizuka K, Goto Y, Inoue H. Dual-strand tumor-suppressor microRNA-145 (miR-145–5p and miR-145–3p) coordinately targeted MTDH in lung squamous cell carcinoma. Oncotarget. 2016;7:72084–98.CrossRef
31.
Mastroianni J, Stickel N, Andrlova H, Hanke K, Melchinger W, Duquesne S, Schmidt D, Falk M, Andrieux G, Pfeifer D, et al. miR-146a controls immune response in the melanoma microenvironment. Cancer Res. 2019;79:183–95.CrossRef
32.
Xi J, Huang Q, Wang L, Ma X, Deng Q, Kumar M, Zhou Z, Li L, Zeng Z, Young KH, et al. miR-21 depletion in macrophages promotes tumoricidal polarization and enhances PD-1 immunotherapy. Oncogene. 2018;37:3151–65.CrossRef
33.
Hsu JM, Xia W, Hsu YH, Chan LC, Yu WH, Cha JH, Chen CT, Liao HW, Kuo CW, Khoo KH, et al. STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion. Nat Commun. 2018;9:1908.CrossRef
34.
Atsaves V, Tsesmetzis N, Chioureas D, Kis L, Leventaki V, Drakos E, Panaretakis T, Grander D, Medeiros LJ, Young KH, Rassidakis GZ. PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma. Leukemia. 2017;31:1633–7.CrossRef
35.
Chan LC, Li CW, Xia W, Hsu JM, Lee HH, Cha JH, Wang HL, Yang WH, Yen EY, Chang WC, et al. IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion. J Clin Invest. 2019;129:3324–38.CrossRef
36.
Vannini A, Leoni V, Barboni C, Sanapo M, Zaghini A, Malatesta P, Campadelli-Fiume G. Gianni T: alphavbeta3-integrin regulates PD-L1 expression and is involved in cancer immune evasion. Proc Natl Acad Sci U S A. 2019;116:20141–50.CrossRef
37.
Lu C, Talukder A, Savage NM, Singh N, Liu K. JAK-STAT-mediated chronic inflammation impairs cytotoxic T lymphocyte activation to decrease anti-PD-1 immunotherapy efficacy in pancreatic cancer. Oncoimmunology. 2017;6:e1291106.CrossRef
38.
Mace TA, Ameen Z, Collins A, Wojcik S, Mair M, Young GS, Fuchs JR, Eubank TD, Frankel WL, Bekaii-Saab T, et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner. Cancer Res. 2013;73:3007–18.CrossRef
39.
McMichael EL, Jaime-Ramirez AC, Guenterberg KD, Luedke E, Atwal LS, Campbell AR, Hu Z, Tatum AS, Kondadasula SV, Mo X, et al. IL-21 enhances natural killer cell response to Cetuximab-coated pancreatic tumor cells. Clin Cancer Res. 2017;23:489–502.CrossRef
Metadata
Title
LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis
Authors
Hao Zhang
Changhao Zhu
Zhiwei He
Shiyu Chen
Lin Li
Chengyi Sun
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2020
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-020-01687-8

Other articles of this Issue 1/2020

Journal of Experimental & Clinical Cancer Research 1/2020 Go to the issue

Research

Synergistic antitumor interaction of valproic acid and simvastatin sensitizes prostate cancer to docetaxel by targeting CSCs compartment via YAP inhibition

Research

NCSTN promotes hepatocellular carcinoma cell growth and metastasis via β-catenin activation in a Notch1/AKT dependent manner

Research

Histone tail analysis reveals H3K36me2 and H4K16ac as epigenetic signatures of diffuse intrinsic pontine glioma

Review

Targeting tumor hypoxia and mitochondrial metabolism with anti-parasitic drugs to improve radiation response in high-grade gliomas

Research

microRNA-96 promotes occurrence and progression of colorectal cancer via regulation of the AMPKα2-FTO-m6A/MYC axis

Research

Autophagic flux inhibition enhances cytotoxicity of the receptor tyrosine kinase inhibitor ponatinib
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits