Human Cell

pp 1–9 | Cite as

Up-regulation of long non-coding RNA AWPPH inhibits proliferation and invasion of gastric cancer cells via miR-203a/DKK2 axis

  • Lei LiEmail author
  • Jiguang Kou
  • Bibo Zhong
Research Article


AWPPH is a newly discovered long non-coding RNA (lncRNA). However, the expression and function of AWPPH in gastric cancer (GC) have not yet been clarified. This study tries to assess the expression and biological roles of AWPPH in GC and the underlying mechanism. The expression of lncRNA AWPPH was evaluated in GC tissues and adjacent normal tissues from 40 patients. Cell Counting Kit-8 (CCK8) and transwell assays were applied to assess cell proliferation and invasion capabilities. Bioinformatics tool was employed to predict AWPPH’s sponging miRNA, while luciferase reporter assays were used to verify the target. LncRNA AWPPH was remarkably downregulated in GC and associated with metastasis. CCK8 and transwell assays proved that AWPPH inhibited cell proliferation and invasion in GC cells. MiR-203a was a predicted and further verified target of AWPPH. DKK2 was verified as a direct target of miR-203a. Upregulation of miR-203a attenuated the repressive effects of AWPPH on GC cell proliferation and invasion. AWPPH inhibited GC cell proliferation and invasion via miR-203a/DKK2 axis. This finding might provide new insight for the potential therapeutic strategies for GC in the future.


Gastric cancer AWPPH miR-203a DKK2 Progression 


Author contributions

LL performed the experiments. JK and BZ analyzed the data. LL designed the study and drafted the manuscript.



Compliance with ethical standards

Conflict of interest

The authors have declared that no competing interests exist.


  1. 1.
    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRefGoogle Scholar
  2. 2.
    Russo AE, Strong VE. Gastric cancer etiology and management in Asia and the West. Annu Rev Med. 2019;70:353–67.CrossRefGoogle Scholar
  3. 3.
    Hanazaki K, Sodeyama H, Wakabayashi M, et al. Surgical treatment of gastric cancer detected by mass screening. Hepatogastroenterology. 1997;44:1126–32.Google Scholar
  4. 4.
    Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. The Lancet. 2016;388:2654–64.CrossRefGoogle Scholar
  5. 5.
    Lee J, Lim DH, Kim S, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012;30:268–73.CrossRefGoogle Scholar
  6. 6.
    Maruyama R, Suzuki H. Long noncoding RNA involvement in cancer. BMB Rep. 2012;45:604–11.CrossRefGoogle Scholar
  7. 7.
    Wright CM, Kirschner MB, Cheng YY, et al. Long non coding RNAs (lncRNAs) are dysregulated in malignant pleural mesothelioma (MPM). PLoS One. 2013;8:e70940.CrossRefGoogle Scholar
  8. 8.
    Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11:228–34.CrossRefGoogle Scholar
  9. 9.
    Chen Y, Yu X, Xu Y, Shen H. Identification of dysregulated lncRNAs profiling and metastasis-associated lncRNAs in colorectal cancer by genome-wide analysis. Cancer Med. 2017;6:2321–30.CrossRefGoogle Scholar
  10. 10.
    Lu PW, Li L, Wang F, Gu YT. Effects of long non-coding RNA HOST2 on cell migration and invasion by regulating MicroRNA let-7b in breast cancer. J Cell Biochem. 2018;119:4570–80.CrossRefGoogle Scholar
  11. 11.
    Shi X, Wang X, Hua Y. LncRNA GACAT1 promotes gastric cancer cell growth, invasion and migration by regulating MiR-149-mediated Of ZBTB2 and SP1. J Cancer. 2018;9:3715–22.CrossRefGoogle Scholar
  12. 12.
    Li C, Chen J, Zhang K, Feng B, Wang R, Chen L. Progress and prospects of long noncoding RNAs (lncRNAs) in hepatocellular carcinoma. Cell Physiol Biochem. 2015;36:423–34.CrossRefGoogle Scholar
  13. 13.
    Wang Y, Gao S, Liu G, Jia R, Fan D, Feng X. Microarray expression profile analysis of long non-coding RNAs in human gastric cardiac adenocarcinoma. Cell Physiol Biochem. 2014;33:1225–38.CrossRefGoogle Scholar
  14. 14.
    Rangel LB, Sherman-Baust CA, Wernyj RP, Schwartz DR, Cho KR, Morin PJ. Characterization of novel human ovarian cancer-specific transcripts (HOSTs) identified by serial analysis of gene expression. Oncogene. 2003;22:7225–32.CrossRefGoogle Scholar
  15. 15.
    Xiao G, Yao J, Kong D, et al. The long noncoding RNA TTTY15, which is located on the Y chromosome, promotes prostate cancer progression by sponging let-7. Eur Urol. 2018;76:315–26.CrossRefGoogle Scholar
  16. 16.
    Li X, Yan X, Wang F, et al. Down-regulated lncRNA SLC25A5-AS1 facilitates cell growth and inhibits apoptosis via miR-19a-3p/PTEN/PI3K/AKT signalling pathway in gastric cancer. J Cell Mol Med. 2019;23:2920–32.CrossRefGoogle Scholar
  17. 17.
    Liu Q, Xiao Y, Cai P, Li J, Li D. Long noncoding RNA DINO (damage induced noncoding) represses the development of gastric cancer by modulating p21 and Bcl-2 associated X protein (Bax) expression. J Cell Biochem. 2019;120:11190–5.CrossRefGoogle Scholar
  18. 18.
    Zhang K, Lu C, Huang X, et al. Long noncoding RNA AOC4P regulates tumor cell proliferation and invasion by epithelial-mesenchymal transition in gastric cancer. Therap Adv Gastroenterol. 2019;12:1756284819827697.Google Scholar
  19. 19.
    Gong P, Qiao F, Wu H, et al. LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer. Cell Death Dis. 2018;9:1158.CrossRefGoogle Scholar
  20. 20.
    Zhao X, Liu Y, Yu S. Long noncoding RNA AWPPH promotes hepatocellular carcinoma progression through YBX1 and serves as a prognostic biomarker. Biochim Biophys Acta. 2017;1863:1805–16.CrossRefGoogle Scholar
  21. 21.
    Wang K, Li X, Song C, Li M. LncRNA AWPPH promotes the growth of triple-negative breast cancer by up-regulating frizzled homolog 7 (FZD7). Biosci Rep. 2018;38:BSR20181223.CrossRefGoogle Scholar
  22. 22.
    Zhu F, Zhang X, Yu Q, et al. LncRNA AWPPH inhibits SMAD4 via EZH2 to regulate bladder cancer progression. J Cell Biochem. 2018;119:4496–505.CrossRefGoogle Scholar
  23. 23.
    Shao YC, Nie XC, Song GQ, Wei Y, Xia P, Xu XY. Prognostic value of DKK2 from the Dickkopf family in human breast cancer. Int J Oncol. 2018;53:2555–65.Google Scholar
  24. 24.
    Brott BK, Sokol SY. Regulation of Wnt/LRP signaling by distinct domains of Dickkopf proteins. Mol Cell Biol. 2002;22:6100–10.CrossRefGoogle Scholar
  25. 25.
    Wang L, Wang H, Duan X, Dai P, Li J. Comprehensive analysis of the canonical and non-canonical Wnt signaling pathways in gastric cancer. Dig Dis Sci. 2019;. Scholar
  26. 26.
    Wang H, Duan XL, Qi XL, et al. Concurrent hypermethylation of SFRP2 and DKK2 Activates the Wnt/beta-catenin pathway and is associated with poor prognosis in patients with gastric cancer. Mol Cells. 2017;40:45–53.CrossRefGoogle Scholar
  27. 27.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.CrossRefGoogle Scholar
  28. 28.
    Lu W, Xu Y, Xu J, Wang Z, Ye G. Identification of differential expressed lncRNAs in human thyroid cancer by a genome-wide analyses. Cancer Med. 2018;7:3935–44.CrossRefGoogle Scholar
  29. 29.
    Gao Y, Meng H, Liu S, et al. LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b. Hum Mol Genet. 2015;24:841–52.CrossRefGoogle Scholar
  30. 30.
    Yang Z, Liu D, Wu D, Liu F, Liu C. The biological function of long noncoding RNA FAL1 in oesophageal carcinoma cells. Artif Cells Nanomed Biotechnol. 2019;47:896–903.CrossRefGoogle Scholar
  31. 31.
    Zhao X, Liu Y, Yu S. Long noncoding RNA AWPPH promotes hepatocellular carcinoma progression through YBX1 and serves as a prognostic biomarker. Biochim Biophys Acta (BBA) Mol Basis Dis. 2017;1863:1805–16.CrossRefGoogle Scholar
  32. 32.
    Yang M, Zhang L, Wang X, Zhou Y, Wu S. Down-regulation of miR-203a by lncRNA PVT1 in multiple myeloma promotes cell proliferation. Arch Med Sci. 2018;14:1333–9.CrossRefGoogle Scholar
  33. 33.
    Zang J, Hui L, Yang N, Yang B, Jiang X. Downregulation of MiR-203a disinhibits Bmi1 and promotes growth and proliferation of keratinocytes in cholesteatoma. Int J Med Sci. 2018;15:447–55.CrossRefGoogle Scholar
  34. 34.
    Wang L, Tong D, Guo Q, et al. HOXD3 targeted by miR-203a suppresses cell metastasis and angiogenesis through VEGFR in human hepatocellular carcinoma cells. Sci Rep. 2018;8:2431.CrossRefGoogle Scholar
  35. 35.
    Zhu J, Zhang S, Gu L, Di W. Epigenetic silencing of DKK2 and Wnt signal pathway components in human ovarian carcinoma. Carcinogenesis. 2012;33:2334–43.CrossRefGoogle Scholar
  36. 36.
    Shen T, Chen Z, Qiao J, Sun X, Xiao Q. Neutralizing monoclonal antibody against Dickkopf2 impairs lung cancer progression via activating NK cells. Cell Death Discov. 2019;5:123.CrossRefGoogle Scholar
  37. 37.
    Deng F, Zhou R, Lin C, et al. Tumor-secreted dickkopf2 accelerates aerobic glycolysis and promotes angiogenesis in colorectal cancer. Theranostics. 2019;9:1001–14.CrossRefGoogle Scholar

Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of GastroenterologyXiaogan Hospital Affiliated of Wuhan University of Science and TechnologyXiaoganPeople’s Republic of China

Personalised recommendations