Skip to main content

Advertisement

Log in

MicroRNA-128 acts as a suppressor in the progression of gastrointestinal stromal tumor by targeting B-lymphoma Mo-MLV insertion region 1

  • RESEARCH ARTICLE
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Introduction

The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism.

Methods

Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed.

Results

We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells.

Conclusion

Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

References

  1. Akahoshi K, Oya M, Koga T, Shiratsuchi Y. Current clinical management of gastrointestinal stromal tumor. World J Gastroenterol. 2018;24:2806–17.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Mulet-Margalef N, Garcia-Del-Muro X. Sunitinib in the treatment of gastrointestinal stromal tumor: patient selection and perspectives. Onco Targets Ther. 2016;9:7573–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nishida T, Goto O, Raut CP, Yahagi N. Diagnostic and treatment strategy for small gastrointestinal stromal tumors. Cancer. 2016;122:3110–8.

    Article  PubMed  Google Scholar 

  4. Mantese G. Gastrointestinal stromal tumor: epidemiology, diagnosis, and treatment. Curr Opin Gastroenterol. 2019;35:555–9.

    Article  CAS  PubMed  Google Scholar 

  5. Pai VD, Demenezes JL, Patil PS, Saklani AP. Multimodality therapy of rectal gastrointestinal stromal tumors in the era of imatinib-an Indian series. J Gastrointest Oncol. 2016;7:262–8.

    PubMed  PubMed Central  Google Scholar 

  6. Tu L, Zhao E, Zhao W, Zhang Z, Tang D, Zhang Y, et al. hsa-miR-376c-3p regulates gastric tumor growth both in vitro and in vivo. Biomed Res Int. 2016;2016:9604257.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Xu DD, Zhou PJ, Wang Y, Zhang Y, Zhang R, Zhang L, et al. miR-150 suppresses the proliferation and tumorigenicity of leukemia stem cells by targeting the Nanog signaling pathway. Front Pharmacol. 2016;7:439.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ching AS, Ahmad-Annuar A. A perspective on the role of microRNA-128 regulation in mental and behavioral disorders. Front Cell Neurosci. 2015;9:465.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Li M, Fu W, Wo L, Shu X, Liu F, Li C. miR-128 and its target genes in tumorigenesis and metastasis. Exp Cell Res. 2013;319:3059–64.

    Article  CAS  PubMed  Google Scholar 

  10. Shang C, Hong Y, Guo Y, Liu YH, Xue YX. miR-128 regulates the apoptosis and proliferation of glioma cells by targeting RhoE. Oncol Lett. 2016;11:904–8.

    Article  CAS  PubMed  Google Scholar 

  11. Zhou XU, Qi L, Tong S, Cui YU, Chen J, Huang T, et al. miR-128 downregulation promotes growth and metastasis of bladder cancer cells and involves VEGF-C upregulation. Oncol Lett. 2015;10:3183–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yao J, Wang C, Dong X, Zhang Y, Li Y, Zhou H, et al. lncRNA SNHG22 sponges miR-128-3p to promote the progression of colorectal cancer by upregulating E2F3. Int J Oncol. 2021. https://doi.org/10.3892/ijo.2021.5251.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ma L, Jiang Y, Wu N. Long non-coding RNA CCL2 promoted gastric cancer function via miR-128/ PARP2 signal pathway. Bioengineered. 2022;13:1602–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bolomsky A, Schlangen K, Schreiner W, Zojer N, Ludwig H. Targeting of BMI-1 with PTC-209 shows potent anti-myeloma activity and impairs the tumour microenvironment. J Hematol Oncol. 2016;9:17.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Li Y, Tian Z, Tan Y, Lian G, Chen S, Chen S, et al. Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer. Mol Cancer. 2020;19:109.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Xu Z, Zhou Z, Zhang J, Xuan F, Fan M, Zhou D, et al. Targeting BMI-1-mediated epithelial-mesenchymal transition to inhibit colorectal cancer liver metastasis. Acta Pharm Sin B. 2021;11:1274–85.

    Article  CAS  PubMed  Google Scholar 

  17. Wang JL, Wu JH, Hong C, Wang YN, Zhou Y, Long ZW, et al. Involvement of Bmi-1 gene in the development of gastrointestinal stromal tumor by regulating p16(Ink4A)/p14(ARF) gene expressions: An in vivo and in vitro study. Pathol Res Pract. 2017;213:1542–51.

    Article  CAS  PubMed  Google Scholar 

  18. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33:459–65.

    Article  PubMed  Google Scholar 

  19. He JH, Han ZP, Zhou JB, Chen WM, Lv YB, He ML, et al. MiR-145 affected the circular RNA expression in prostate cancer LNCaP cells. J Cell Biochem. 2018;119:9168–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jiang H, Ge R, Chen S, Huang L, Mao J, Sheng L. miRNA-204-5p acts as tumor suppressor to influence the invasion and migration of astrocytoma by targeting ezrin and is downregulated by DNA methylation. Bioengineered. 2021;12:9301–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang W, Hong G, Wang S, Gao W, Wang P. Tumor-derived exosomal miRNA-141 promote angiogenesis and malignant progression of lung cancer by targeting growth arrest-specific homeobox gene (GAX). Bioengineered. 2021;12:821–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sun Y, Hou Z, Luo B, Li C, Liu J, Liu J, et al. Circular RNA circRNA_0082835 promotes progression and lymphatic metastasis of primary melanoma by sponging microRNA miRNA-429. Bioengineered. 2021;12:4159–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhu K, Li K, Yuan DW, Xu G, Kang L, Dang CX, et al. Clinicopathological and prognostic significance of expression of B-cell-specific moloney murine leukemia virus insertion site 1 (BMI-1) gene and protein in gastrointestinal stromal tumors. Med Sci Monit. 2018;24:6414–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nanta R, Kumar D, Meeker D, Rodova M, Van Veldhuizen PJ, Shankar S, et al. NVP-LDE-225 (Erismodegib) inhibits epithelial-mesenchymal transition and human prostate cancer stem cell growth in NOD/SCID IL2Rgamma null mice by regulating Bmi-1 and microRNA-128. Oncogenesis. 2013;2: e42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhu Y, Yu F, Jiao Y, Feng J, Tang W, Yao H, et al. Reduced miR-128 in breast tumor-initiating cells induces chemotherapeutic resistance via Bmi-1 and ABCC5. Clin Cancer Res. 2011;17:7105–15.

    Article  CAS  PubMed  Google Scholar 

  26. Jakhetiya A, Garg PK, Prakash G, Sharma J, Pandey R, Pandey D. Targeted therapy of gastrointestinal stromal tumours. World J Gastrointest Surg. 2016;8:345–52.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Cao CL, Niu HJ, Kang SP, Cong CL, Kang SR. miRNA-21 sensitizes gastrointestinal stromal tumors (GISTs) cells to Imatinib via targeting B-cell lymphoma 2 (Bcl-2). Eur Rev Med Pharmacol Sci. 2016;20:3574–81.

    PubMed  Google Scholar 

  28. Liang L, Kang H, Jia J. HCP5 contributes to cisplatin resistance in gastric cancer through miR-128/HMGA2 axis. Cell Cycle. 2021;20:1080–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yang Z, Pu M, Dong X, Yang H, Chang W, Liu T, et al. CTCF-activated SNHG16 facilitates gastrointestinal stromal tumor by targeting miR-128-3p/CASC3 axis. Exp Cell Res. 2022;417: 113131.

    Article  CAS  PubMed  Google Scholar 

  30. Godlewski J, Nowicki MO, Bronisz A, Williams S, Otsuki A, Nuovo G, et al. Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008;68:9125–30.

    Article  CAS  PubMed  Google Scholar 

  31. Fang W, Shi C, Wang Y, Song J, Zhang L. microRNA-128-3p inhibits CD4+ regulatory T cells enrichment by targeting interleukin 16 in gastric cancer. Bioengineered. 2022;13:1025–38.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang Z, Bu X, Chen H, Wang Q, Sha W. Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin. Int J Mol Med. 2016;38:1199–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhou L, Zhang WG, Wang DS, Tao KS, Song WJ, Dou KF. MicroRNA-183 is involved in cell proliferation, survival and poor prognosis in pancreatic ductal adenocarcinoma by regulating Bmi-1. Oncol Rep. 2014;32:1734–40.

    Article  CAS  PubMed  Google Scholar 

  34. Ling Z, Zhang J, Liu Q. Oncogenic Forkhead box D3 antisense RNA 1 promotes cell survival and confers temozolomide resistance in glioblastoma cells through the miR-128-3p/WEE1 G2 checkpoint kinase axis. Bioengineered. 2022;13:6012–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sun X, Yang Z, Zhang Y, He J, Wang F, Su P, et al. Prognostic implications of tissue and serum levels of microRNA-128 in human prostate cancer. Int J Clin Exp Pathol. 2015;8:8394–401.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Allegra E, Puzzo L, Zuccala V, Trapasso S, Vasquez E, Garozzo A, et al. Nuclear BMI-1 expression in laryngeal carcinoma correlates with lymph-node pathological status. World J Surg Oncol. 2012;10:206.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bai C, Liu X, Xu J, Qiu C, Wang R, Zheng J. Expression profiles of stemness genes in gastrointestinal stromal tumor. Hum Pathol. 2018;76:76–84.

    Article  CAS  PubMed  Google Scholar 

  38. Tian Z, Guo B, Yu M, Wang C, Zhang H, Liang Q, et al. Upregulation of micro-ribonucleic acid-128 cooperating with downregulation of PTEN confers metastatic potential and unfavorable prognosis in patients with primary osteosarcoma. Onco Targets Ther. 2014;7:1601–8.

    PubMed  PubMed Central  Google Scholar 

  39. Wang MC, Li CL, Cui J, Jiao M, Wu T, Jing LI, et al. BMI-1, a promising therapeutic target for human cancer. Oncol Lett. 2015;10:583–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Venkataraman S, Alimova I, Fan R, Harris P, Foreman N, Vibhakar R. MicroRNA 128a increases intracellular ROS level by targeting Bmi-1 and inhibits medulloblastoma cancer cell growth by promoting senescence. PLoS ONE. 2010;5: e10748.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Hu X, Xu M, Hu Y, Li N, Zhou L. B7–H3, negatively regulated by miR-128, promotes colorectal cancer cell proliferation and migration. Cell Biochem Biophys. 2021;79:397–405.

    Article  CAS  PubMed  Google Scholar 

  42. Zhao L, Li R, Xu S, Li Y, Zhao P, Dong W, et al. Tumor suppressor miR-128-3p inhibits metastasis and epithelial-mesenchymal transition by targeting ZEB1 in esophageal squamous-cell cancer. Acta Biochim Biophys Sin (Shanghai). 2018;50:171–80.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This study was supported by National Natural Science Foundation of China (No. 81960445), Natural Science Foundation of Inner Mongolia Autonomous Region (2020LH08005, 2018LH08081, 2015MS0854), Inner Mongolia Autonomous Region Science and Technology Plan Project (No. 20180317), and Baotou Science and Technology Plan Project (2019Z3011-04, 2019P3078, 2017S2001-5-03).

Author information

Authors and Affiliations

Authors

Contributions

JW, CW, and XC wrote the paper; LL, LW, and JW conceived the experiments; XX analyzed the data; TD collected and provided the sample for this study. All authors have read and approved the final submitted manuscript.

Corresponding author

Correspondence to Tong Dang.

Ethics declarations

Conflict of interest

The authors declare no competing financial interest.

Ethics approval and consent to participate

The informed consents were obtained from family of patients, and this study was approved by the Ethical Committee of The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology (Approved No. 2019LW-001).

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 18 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, J., Wang, C., Cui, X. et al. MicroRNA-128 acts as a suppressor in the progression of gastrointestinal stromal tumor by targeting B-lymphoma Mo-MLV insertion region 1. Clin Transl Oncol 26, 363–374 (2024). https://doi.org/10.1007/s12094-023-03354-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-023-03354-8

Keywords

Navigation