Digestive Diseases and Sciences

, Volume 64, Issue 10, pp 2823–2829 | Cite as

miR-9-5p Suppresses Malignant Biological Behaviors of Human Gastric Cancer Cells by Negative Regulation of TNFAIP8L3

  • Yanyun Fan
  • Ying Shi
  • Zhenhe Lin
  • Xiaoxiao Huang
  • Jinying Li
  • Wei Huang
  • Dongyan ShenEmail author
  • Guohong ZhuangEmail author
  • Wenming LiuEmail author
Original Article



MicroRNA is essential for the malignant progression of human gastric cancer (GC), which is a leading cause of cancer deaths. However, the mechanism is still not so clear.


In our present research, we investigated the effect of miR-9-5p in GC.


We detected miR-9-5p expression in human gastric epithelial cell (GES-1) and GC cells (AGS, BGC-823, MKN-45, and MGC-803), plasma of normal or GC patients, as well as orthotopic xenograft mouse models by real-time PCR. The migration ability was detected by Transwell assays after miR-9-5p mimic or inhibitor transfection in GC cells.


Our results showed that miR-9-5p expression in GC cells and plasma was significantly decreased. miR-9-5p inhibited migration of GC cells by regulating TNFAIP8L3 directly. Low expression of miR-9-5p in GC patients hardly suppressed the migration mediated by TNFAIP8L3.


miR-9-5p, as a potential tumor suppressor gene, is closely related to the malignant progression of GC. Exploring the regulation between miR-9-5p and TNFAIP8L3 may provide a novel strategy for GC treatment.


miR-9-5p TNFAIP8L3 Gastric cancer Migration 3′UTR 



This research was supported by the Youth Research Project of Health and Family Planning Commission of Fujian Province, China (No. 2015-2-48), Natural Science Foundation of Guangdong Province, China (No. 2018A0303130302), Medical Research Fund of Guangdong Province, China (No. A2018011), and Science Foundation for The Excellent Youth Scholars of Jinan University, China (Nos. 89018021 and 21618302).

Author's contribution

WML, GHS, and DYS conceived the project. WML and GHS designed the experiments; YYF, YS, ZHL, XXH, JYL, and WH performed the experiments; and YS and WML wrote the paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals and informed consent

All samples were obtained with patients’ informed consent. The Ethics Committee of Zhongshan Hospital, Xiamen University and The First Affiliated Hospital, Jinan University approved this study. This study does not involve animals.


  1. 1.
    Rugge M, Genta RM, Graham DY, et al. Chronicles of a cancer foretold: 35 years of gastric cancer risk assessment. Gut. 2016;65:721–725.CrossRefPubMedGoogle Scholar
  2. 2.
    Chen W, Zheng R, Zhang S, et al. The incidences and mortalities of major cancers in China, 2009. Chin J Cancer. 2013;32:106–112.CrossRefPubMedGoogle Scholar
  3. 3.
    Cancer Genome Atlas Research, N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209.CrossRefGoogle Scholar
  4. 4.
    Zamore PD, Haley B. Ribo-gnome: the big world of small RNAs. Science. 2005;309:1519–1524.CrossRefPubMedGoogle Scholar
  5. 5.
    Paladini L, Fabris L, Bottai G, et al. Targeting microRNAs as key modulators of tumor immune response. J Exp Clin Cancer Res. 2016;35:103.CrossRefPubMedGoogle Scholar
  6. 6.
    Tsai MM, Wang CS, Tsai CY, et al. Potential diagnostic, prognostic and therapeutic targets of MicroRNAs in human gastric cancer. Int J Mol Sci. 2016. Scholar
  7. 7.
    Liu J, Wang X, Yang X, et al. miRNA423-5p regulates cell proliferation and invasion by targeting trefoil factor 1 in gastric cancer cells. Cancer Lett. 2014;347:98–104.CrossRefPubMedGoogle Scholar
  8. 8.
    Shi Y, Chen GB, Huang QW, et al. miR218-5p regulates the proliferation of gastric cancer cells by targeting TFF1 in an Erk1/2-dependent manner. Biochim Biophys Acta. 2015;1852:970–979.CrossRefPubMedGoogle Scholar
  9. 9.
    Auer RL. The coming of age of microRNA for B cell lymphomas. Histopathology. 2011;58:39–48.CrossRefPubMedGoogle Scholar
  10. 10.
    Huang X, Zhou X, Wang Z, et al. CD99 triggers upregulation of miR-9-modulated PRDM1/BLIMP1 in Hodgkin/Reed-Sternberg cells and induces redifferentiation. Int J Cancer. 2012;131:E382–E394.CrossRefPubMedGoogle Scholar
  11. 11.
    Laios A, O'Toole S, Flavin R, et al. Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mol Cancer. 2008;7:35.CrossRefPubMedGoogle Scholar
  12. 12.
    Gao HY, Huo FC, Wang HY, et al. MicroRNA-9 inhibits the gastric cancer cell proliferation by targeting TNFAIP8. Cell Prolif. 2017. Scholar
  13. 13.
    Jiao G, Pan B, Zhou Z, et al. MicroRNA-21 regulates cell proliferation and apoptosis in H(2)O(2)-stimulated rat spinal cord neurons. Mol Med Rep. 2015;12:7011–7016.CrossRefPubMedGoogle Scholar
  14. 14.
    Sugita F, Maki K, Nakamura Y, et al. Overexpression of MIR9 indicates poor prognosis in acute lymphoblastic leukemia. Leuk Lymphoma. 2014;55:78–86.CrossRefPubMedGoogle Scholar
  15. 15.
    Han L, Wang W, Ding W, et al. MiR-9 is involved in TGF-beta1-induced lung cancer cell invasion and adhesion by targeting SOX7. J Cell Mol Med. 2017;21:2000–2008.CrossRefPubMedGoogle Scholar
  16. 16.
    Zhao P, Wang L, Xiang X, et al. Increased expression of TIPE2 mRNA in PBMCs of patients with ankylosing spondylitis is negatively associated with the disease severity. Hum Immunol. 2017;78:232–237.CrossRefPubMedGoogle Scholar
  17. 17.
    Kim BG, Gao MQ, Kang S, et al. Mechanical compression induces VEGFA overexpression in breast cancer via DNMT3A-dependent miR-9 downregulation. Cell Death Dis. 2017;8:e2646.CrossRefPubMedGoogle Scholar
  18. 18.
    Lou Y, Liu S. The TIPE (TNFAIP8) family in inflammation, immunity, and cancer. Mol Immunol. 2011;49:4–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Goldsmith JR, Chen YH. Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins. Cell Mol Immunol. 2017;14:482–487.CrossRefPubMedGoogle Scholar
  20. 20.
    Fayngerts SA, Wu J, Oxley CL, et al. TIPE3 is the transfer protein of lipid second messengers that promote cancer. Cancer Cell. 2014;26:465–478.CrossRefPubMedGoogle Scholar
  21. 21.
    Cui J, Hao C, Zhang W, et al. Identical expression profiling of human and murine TIPE3 protein reveals links to its functions. J Histochem Cytochem. 2015;63:206–216.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology, Zhongshan HospitalXiamen UniversityXiamenChina
  2. 2.Department of GastroenterologyThe First Affiliated Hospital, Jinan UniversityGuangzhouChina
  3. 3.The First Clinical Medical CollegeJinan UniversityGuangzhouChina
  4. 4.Organ Transplantation InstituteMedical College of Xiamen UniversityXiamenChina
  5. 5.BiobankThe First Affiliated Hospital of Xiamen UniversityXiamenChina

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