miR-548b-3p functions as a tumor suppressor in lung cancer

  • Zhenlin Wang
  • Xingfu Wu
  • Xiangwei Hou
  • Wenqiu Zhao
  • Cheng YangEmail author
  • Wei WanEmail author
  • Lixia ChenEmail author
Original Article


miR-548-3p is one of the members of miR-548 family, a large primate-specific miRNA gene family. The role of miR-548-3p in lung cancer was less studied. In this study, we found the expression of miR-548-3p was lower both in clinical tumor specimens and lung cancer cells compared with normal controls. In vitro, miR-548-3p inhibited lung cancer cell growth and promoted cell apoptosis at the S stage of cell cycle. The underlying mechanism of miR-548b-3p-induced cell proliferation inhibition and apoptosis may be associated with the inhibition of PI3K/AKT signaling pathway. In vivo, miR-548b-3p also suppressed tumor growth in xenografts model of lung cancer cells. Our results indicated that miR-548b-3p might be an anti-tumor target of lung cancer in the future.


Lung cancer miR-548b-3p PI3K/AKT signaling pathway Tumor suppressor 


Author contribution

Z.l.W, X.f.W. X.w.H. W.q.Z., and C.Y. conducted the experiments and provided experimental methods and data. Z.l.W, W.W., and L.x.C. designed the study, analyzed the data, and wrote the manuscript.

Funding information

This work was supported by Shanghai Municipal Planning Commission of Science and Research (201840209).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experimental protocols and methods were approved by the XuZhou City Hospital of Medical College of TCM, No 20190422. We also confirmed that all methods were performed in accordance with the relevant guidelines and regulations. Mice were bred in the Animal Core Facility by following the procedures approved by the XuZhou City Hospital of Medical College of Institutional Animal Care and Use Committee.


  1. 1.
    Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, Znaor A, Bray F (2019) Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 144:1941–1953Google Scholar
  2. 2.
    Kanodra NM, Silvestri GA, Tanner NT (2015) Screening and early detection efforts in lung cancer. Cancer 121:1347–1356CrossRefGoogle Scholar
  3. 3.
    Wu KL, Tsai YM, Lien CT, Kuo PL, Hung AJ (2019) The Roles of MicroRNA in Lung Cancer. Int J Mol Sci 20, 1–25Google Scholar
  4. 4.
    Fan L, Qi H, Teng J, Su B, Chen H, Wang C, Xia Q (2016) Identification of serum miRNAs by nano-quantum dots microarray as diagnostic biomarkers for early detection of non-small cell lung cancer. Tumour Biol 37:7777–7784CrossRefGoogle Scholar
  5. 5.
    Zhang YK, Zhu WY, He JY, Chen DD, Huang YY, Le HB, Liu XG (2012) miRNAs expression profiling to distinguish lung squamous-cell carcinoma from adenocarcinoma subtypes. J Cancer Res Clin Oncol 138:1641–1650CrossRefGoogle Scholar
  6. 6.
    Su W et al (2016) miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1. Biomed Pharmacother 84:123–129CrossRefGoogle Scholar
  7. 7.
    Jin Z, Guan L, Song Y, Xiang GM, Chen SX, Gao B (2016) MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition. Eur Rev Med Pharmacol Sci 20:1080–1086Google Scholar
  8. 8.
    Bica-Pop C, Cojocneanu-Petric R, Magdo L, Raduly L, Gulei D, Berindan-Neagoe I (2018) Overview upon miR-21 in lung cancer: focus on NSCLC. Cell Mol Life Sci 75:3539–3551CrossRefGoogle Scholar
  9. 9.
    Tian Y, Sun C, Zhang L, Pan Y (2018) Clinical significance of miRNA - 106a in non-small cell lung cancer patients who received cisplatin combined with gemcitabine chemotherapy. Cancer Biol Med 15:157–164CrossRefGoogle Scholar
  10. 10.
    Zhang H, Hu B, Wang Z, Zhang F, Wei H, Li L (2017) miR-181c contributes to cisplatin resistance in non-small cell lung cancer cells by targeting Wnt inhibition factor 1. Cancer Chemother Pharmacol 80:973–984CrossRefGoogle Scholar
  11. 11.
    Arechaga-Ocampo E, Lopez-Camarillo C, Villegas-Sepulveda N, Gonzalez-De la Rosa CH, Perez-Añorve IX, Roldan-Perez R, Flores-Perez A, Peña-Curiel O, Angeles-Zaragoza O, Rangel Corona R, Gonzalez-Barrios JA, Bonilla-Moreno R, Del Moral-Hernandez O, Herrera LA, Garcia-Carranca A (2017) Tumor suppressor miR-29c regulates radioresistance in lung cancer cells. Tumour Biol 39, 1–14Google Scholar
  12. 12.
    He Z, Liu Y, Xiao B, Qian X (2015) miR-25 modulates NSCLC cell radio-sensitivity through directly inhibiting BTG2 expression. Biochem Biophys Res Commun 457:235–241CrossRefGoogle Scholar
  13. 13.
    Liu YJ, Lin YF, Chen YF, Luo EC, Sher YP, Tsai MH, Chuang EY, Lai LC (2013) MicroRNA-449a enhances radiosensitivity in CL1-0 lung adenocarcinoma cells. PLoS One 8:e62383CrossRefGoogle Scholar
  14. 14.
    Liang T, Guo L, Liu C (2012) Genome-wide analysis of mir-548 gene family reveals evolutionary and functional implications. J Biomed Biotechnol 2012:679563CrossRefGoogle Scholar
  15. 15.
    Hu B et al (2014) Identification of a tumor-suppressive human-specific microRNA within the FHIT tumor-suppressor gene. Cancer Res 74:2283–2294CrossRefGoogle Scholar
  16. 16.
    Shi Y, Qiu M, Wu Y, Hai L (2015) MiR-548-3p functions as an anti-oncogenic regulator in breast cancer. Biomed Pharmacother 75:111–116CrossRefGoogle Scholar
  17. 17.
    Ni XF, Zhao LH, Li G, Hou M, Su M, Zou CL, Deng X (2018) MicroRNA-548-3p and MicroRNA-576-5p enhance the migration and invasion of esophageal squamous cell carcinoma cells via NRIP1 down-regulation. Neoplasma 65:881–887CrossRefGoogle Scholar
  18. 18.
    Xie Q, Wen H, Zhang Q, Zhou W, Lin X, Xie D, Liu Y (2017) Inhibiting PI3K-AKt signaling pathway is involved in antitumor effects of ginsenoside Rg3 in lung cancer cell. Biomed Pharmacother 85:16–21CrossRefGoogle Scholar
  19. 19.
    Jiang JH, Pi J, Jin H, Cai JY (2019) Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways. J Cell Biochem 120:3736–3746CrossRefGoogle Scholar
  20. 20.
    Aziz, A.U.R., Farid, S., Qin, K., Wang, H. and Liu, B. (2018). PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation ofOvarian Cancer. Biomolecules 8, 1–14Google Scholar
  21. 21.
    Shen, W.M., Yin, J.N., Xu, R.J., Xu, D.F. and Zheng, S.Y. (2019). Ubiquitin specific peptidase 49 inhibits non-small cell lung cancer cell growth bysuppressing PI3K/AKT signaling. Kaohsiung J Med Sci 35. 401–407Google Scholar
  22. 22.
    Guo C, Wang L, Zhao Y, Jiang B, Luo J, Shi D (2019) BOS-93, a novel bromophenol derivative, induces apoptosis and autophagy in human A549 lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathway. Exp Ther Med 17:3848–3858Google Scholar
  23. 23.
    Zhao W et al (2018) MiR-320a-3p/ELF3 axis regulates cell metastasis and invasion in non-small cell lung cancer via PI3K/Akt pathway. Gene 670:31–37CrossRefGoogle Scholar
  24. 24.
    Sun DM, Tang BF, Li ZX, Guo HB, Cheng JL, Song PP, Zhao X (2018) MiR-29c reduces the cisplatin resistance of non-small cell lung cancer cells by negatively regulating the PI3K/Akt pathway. Sci Rep 8:8007CrossRefGoogle Scholar
  25. 25.
    Saffari, M., Ghaderian, S.M.H., Omrani, M.D., Afsharpad, M., Shankaie, K. and Samadaian, N. (2018). The Association of miR-let 7b and miR-548 with PTEN in Prostate Cancer. Urol J 16, 267–273Google Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosurgery, Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Xuzhou TCM Hospital Affiliated to Nanjing University of Chinese MedicineXuzhouChina
  3. 3.Department of Orthopedic Oncology, Changzheng HospitalThe Second Military Medical UniversityShanghaiChina

Personalised recommendations