DUXAP8, a Pseudogene Derived LncRNA, Promotes Growth of Pancreatic Carcinoma Cells by Epigenetically Silencing CDKN1A and KLF2

Overview

Journal Cancer Commun (Lond)

Publisher Wiley

Specialty Oncology

Date 2018 Oct 28

PMID 30367681

Citations 43

Authors

Yifan Lian

Jiebin Yang

Yikai Lian

Chuangxing Xiao

Xuezhen Hu

Hongzhi Xu

Affiliations

Soon will be listed here.

Abstract

Background: Recent studies highlight pseudogene derived long non-coding RNAs (lncRNAs) as key regulators of cancer biology. However, few of them have been well characterized in pancreatic cancer. Here, we aimed to identify the association between pseudogene derived lncRNA DUXAP8 and growth of pancreatic cancer cells.

Methods: We screened for pseudogene derived lncRNAs associated with human pancreatic cancer by comparative analysis of three independent datasets from GEO. Quantitative real-time reverse transcription polymerase chain reaction was used to assess the relative expression of DUXAP8 in pancreatic cancer tissues and cells. Loss-of-function approaches were used to investigate the potential functional roles of DUXAP8 in pancreatic cancer cell proliferation and apoptosis in vitro and in vivo. RNA immunoprecipitation, chromosome immunoprecipitation assay and rescue experiments were performed to analyze the association of DUXAP8 with target proteins and genes in pancreatic cancer cells.

Results: Pancreatic cancer tissues had significantly higher DUXAP8 levels than paired adjacent normal tissues. High DUXAP8 expression was associated with a larger tumor size, advanced pathological stage and shorter overall survival of pancreatic cancer patients. Moreover, silencing DUXAP8 expression by siRNA or shRNA inhibited pancreatic cancer cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistic analyses indicated that DUXAP8 regulates PC cell proliferation partly through downregulation of tumor suppressor CDKN1A and KLF2 expression.

Conclusion: Our results suggest that tumor expression of pseudogene derived lncRNA DUXAP8 plays an important role in pancreatic cancer progression. DUXAP8 may serve as a candidate biomarker and represent a novel therapeutic target of pancreatic cancer.

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References

King J, Bouvet M, Singh G, Williams J . Improving theranostics in pancreatic cancer. J Surg Oncol. 2017; 116(1):104-113. PMC: 5520663. DOI: 10.1002/jso.24625. View

Ding J, Xie M, Lian Y, Zhu Y, Peng P, Wang J . Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer. Oncogenesis. 2017; 6(1):e288. PMC: 5294247. DOI: 10.1038/oncsis.2016.84. View

Lian Y, Wang J, Feng J, Ding J, Ma Z, Li J . Long non-coding RNA IRAIN suppresses apoptosis and promotes proliferation by binding to LSD1 and EZH2 in pancreatic cancer. Tumour Biol. 2016; 37(11):14929-14937. DOI: 10.1007/s13277-016-5380-8. View

Shi X, Ma C, Zhu Q, Yuan D, Sun M, Gu X . Upregulation of long intergenic noncoding RNA 00673 promotes tumor proliferation via LSD1 interaction and repression of NCALD in non-small-cell lung cancer. Oncotarget. 2016; 7(18):25558-75. PMC: 5041926. DOI: 10.18632/oncotarget.8338. View

Sun M, Nie F, Zang C, Wang Y, Hou J, Wei C . The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB. Mol Ther. 2017; 25(3):739-751. PMC: 5363203. DOI: 10.1016/j.ymthe.2016.12.018. View

Xu T, Liu X, Xia R, Yin L, Kong R, Chen W . SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer. Oncogene. 2015; 34(45):5648-61. DOI: 10.1038/onc.2015.18. View

Grander D, Johnsson P . Pseudogene-Expressed RNAs: Emerging Roles in Gene Regulation and Disease. Curr Top Microbiol Immunol. 2015; 394:111-26. DOI: 10.1007/82_2015_442. View

Yamaguchi H, Hung M . Regulation and Role of EZH2 in Cancer. Cancer Res Treat. 2014; 46(3):209-22. PMC: 4132442. DOI: 10.4143/crt.2014.46.3.209. View

Popova E, Pinzon-Guzman C, Salzberg A, Zhang S, Barnstable C . LSD1-Mediated Demethylation of H3K4me2 Is Required for the Transition from Late Progenitor to Differentiated Mouse Rod Photoreceptor. Mol Neurobiol. 2015; 53(7):4563-81. PMC: 6910084. DOI: 10.1007/s12035-015-9395-8. View

10.

Wolfgang C, Herman J, Laheru D, Klein A, Erdek M, Fishman E . Recent progress in pancreatic cancer. CA Cancer J Clin. 2013; 63(5):318-48. PMC: 3769458. DOI: 10.3322/caac.21190. View

11.

Yu G, Yao W, Gumireddy K, Li A, Wang J, Xiao W . Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression. Mol Cancer Ther. 2014; 13(12):3086-97. PMC: 4265235. DOI: 10.1158/1535-7163.MCT-14-0245. View

12.

Scarola M, Comisso E, Pascolo R, Chiaradia R, Marion R, Schneider C . Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA. Nat Commun. 2015; 6:7631. PMC: 4510692. DOI: 10.1038/ncomms8631. View

13.

Yoo K, Hennighausen L . EZH2 methyltransferase and H3K27 methylation in breast cancer. Int J Biol Sci. 2012; 8(1):59-65. PMC: 3226033. DOI: 10.7150/ijbs.8.59. View

14.

Poliseno L, Marranci A, Pandolfi P . Pseudogenes in Human Cancer. Front Med (Lausanne). 2015; 2:68. PMC: 4585173. DOI: 10.3389/fmed.2015.00068. View

15.

Hayashi H, Arao T, Togashi Y, Kato H, Fujita Y, de Velasco M . The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer. Oncogene. 2013; 34(2):199-208. DOI: 10.1038/onc.2013.547. View

16.

Harrow J, Frankish A, Gonzalez J, Tapanari E, Diekhans M, Kokocinski F . GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012; 22(9):1760-74. PMC: 3431492. DOI: 10.1101/gr.135350.111. View

17.

Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108. DOI: 10.3322/caac.21262. View

18.

Pink R, Carter D . Pseudogenes as regulators of biological function. Essays Biochem. 2013; 54:103-12. DOI: 10.1042/bse0540103. View

19.

Shi Y, Lan F, Matson C, Mulligan P, Whetstine J, Cole P . Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004; 119(7):941-53. DOI: 10.1016/j.cell.2004.12.012. View

20.

Wei C, Nie F, Jiang L, Chen Q, Chen Z, Chen X . The pseudogene DUXAP10 promotes an aggressive phenotype through binding with LSD1 and repressing LATS2 and RRAD in non small cell lung cancer. Oncotarget. 2016; 8(3):5233-5246. PMC: 5354904. DOI: 10.18632/oncotarget.14125. View