Biotechnology Letters

, Volume 39, Issue 10, pp 1485–1492 | Cite as

miR-34a attenuates glioma cells progression and chemoresistance via targeting PD-L1

  • Yi Wang
  • Li WangEmail author
Original Research Paper



To investigate the roles of miR-34a in progression and chemoresistance of glioma cells.


Quantitative real-time PCR analysis showed that miR-34a level was lower, but PD-L1 expression level was higher in glioma tissue specimens compared with normal brain tissues and their expression levels were negatively correlated. Ectopic expression of miR-34a inhibited glioma cell proliferation, promoted cell cycle arrest in G1/S phase and cell apoptosis. Additionally, miR-34a/PD-L1 axis was again confirmed and co-expression of PD-L1 with miR-34a mimics attenuated the effects of miR-34a on cell proliferation and apoptosis in glioma cells. Importantly, PD-L1 overexpression resulted in chemoresistance in glioma cells, this effect was attenuated by miR-34a overexpression.


miR-34a inhibits glioma cells progression and chemoresistance via targeting PD-L1.


Drug resistance Glioma miR-34a Paclitaxel PD-L1 


  1. Bozeman EN, He S, Shafizadeh Y, Selvaraj P (2016) Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12. Hum Vaccin Immunother 12:421–430CrossRefPubMedGoogle Scholar
  2. Chen J, Jiang CC, Jin L, Zhang XD (2016) Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Ann Oncol 27:409–416CrossRefPubMedGoogle Scholar
  3. Chen S, Wang RX, Liu Y, Yang WT, Shao ZM (2017) PD-L1 expression of the residual tumor serves as a prognostic marker in local advanced breast cancer after neoadjuvant chemotherapy. Int J Cancer 140:1384–1395CrossRefPubMedGoogle Scholar
  4. Cortez MA, Ivan C, Valdecanas D, Wang X, Peltier HJ, Ye Y, Araujo L, Carbone DP, Shilo K, Giri DK et al (2016) PDL1 regulation by p53 via miR-34. J Natl Cancer Inst. doi: 10.1093/jnci/djv303 PubMedGoogle Scholar
  5. Feld E, Horn L (2016) Targeting PD-L1 for non-small-cell lung cancer. Immunotherapy 8:747–758CrossRefPubMedGoogle Scholar
  6. Gao H, Zhao H, Xiang W (2013) Expression level of human miR-34a correlates with glioma grade and prognosis. J Neurooncol 113:221–228CrossRefPubMedGoogle Scholar
  7. Hardcastle J, Mills L, Malo CS, Jin F, Kurokawa C, Geekiyanage H, Schroeder M, Sarkaria J, Johnson AJ, Galanis E (2016) Immunovirotherapy with measles virus strains in combination with anti-PD-1 antibody blockade enhances antitumor activity in glioblastoma treatment. Neuro Oncol 19:493–502Google Scholar
  8. Kessler T, Sahm F, Blaes J, Osswald M, Rubmann P, Milford D, Urban S, Jestaedt L, Heiland S, Bendszus M et al (2015) Glioma cell VEGFR-2 confers resistance to chemotherapeutic and antiangiogenic treatments in PTEN-deficient glioblastoma. Oncotarget 6:31050–31068CrossRefPubMedPubMedCentralGoogle Scholar
  9. Moroishi T, Hayashi T, Pan WW, Fujita Y, Holt MV, Qin J, Carson DA, Guan KL (2016) The hippo pathway kinases LATS1/2 suppress cancer immunity. Cell 167(1525–1539):e1517Google Scholar
  10. Ock CY, Kim S, Keam B, Kim M, Kim TM, Kim JH, Jeon YK, Lee JS, Kwon SK, Hah JH et al (2016) PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Oncotarget 7:15901–15914CrossRefPubMedPubMedCentralGoogle Scholar
  11. Pessina A, Bonomi A, Cocce V, Invernici G, Navone S, Cavicchini L, Sisto F, Ferrari M, Vigano L, Locatelli A et al (2011) Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy. PLoS ONE 6:e28321CrossRefPubMedPubMedCentralGoogle Scholar
  12. Sagiv-Barfi I, Kohrt HE, Czerwinski DK, Ng PP, Chang BY, Levy R (2015) Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK. Proc Natl Acad Sci USA 112:E966–E972CrossRefPubMedPubMedCentralGoogle Scholar
  13. Sun L, Wu Z, Shao Y, Pu Y, Miu W, Yao J, Wu Y, Yang Z (2012) MicroRNA-34a suppresses cell proliferation and induces apoptosis in U87 glioma stem cells. Technol Cancer Res Treat 11:483–490CrossRefPubMedGoogle Scholar
  14. Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, Di Cunto F et al (2011) Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147:344–357CrossRefPubMedPubMedCentralGoogle Scholar
  15. Teng F, Meng X, Wang X, Yuan J, Liu S, Mu D, Zhu H, Kong L, Yu J (2016) Expressions of CD8 + TILs, PD-L1 and Foxp3 + TILs in stage I NSCLC guiding adjuvant chemotherapy decisions. Oncotarget 7:64318–64329CrossRefPubMedPubMedCentralGoogle Scholar
  16. Tsao MS, Le Teuff G, Shepherd FA, Landais C, Hainaut P, Filipits M, Pirker R, Le Chevalier T, Graziano S, Kratze R et al (2017) PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer. Ann Oncol 28:882–889CrossRefPubMedGoogle Scholar
  17. Wang X, Li J, Dong K, Lin F, Long M, Ouyang Y, Wei J, Chen X, Weng Y, He T et al (2015) Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia. Cell Signal 27:443–452CrossRefPubMedGoogle Scholar
  18. Zhai L, Ladomersky E, Dostal CR, Lauing KL, Swoap K, Billingham LK, Gritsina G, Wu M, McCusker RH, Binder DC et al (2017) Non-tumor cell IDO1 predominantly contributes to enzyme activity and response to CTLA-4/PD-L1 inhibition in mouse glioblastoma. Brain Behav Immun 62:24–29CrossRefPubMedGoogle Scholar
  19. Zhang X, Zhu S, Li T, Liu YJ, Chen W, Chen J (2017) Targeting immune checkpoints in malignant glioma. Oncotarget 8:7157–7174PubMedGoogle Scholar
  20. Zhou C, Cheng H, Qin W, Zhang Y, Xiong H, Yang J, Huang H, Wang Y, Chen XZ, Tang J (2017) Pygopus2 inhibits the efficacy of paclitaxel-induced apoptosis and induces multidrug resistance in human glioma cells. Oncotarget 8:27915–27928PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  1. 1.Department of NeurosurgeryCangzhou Central HospitalCangzhouChina
  2. 2.Department of OncologyThe Third Affiliated Hospital of Hebei Medical UniversityShijiazhuang CityChina

Personalised recommendations