Biotechnology Letters

, Volume 40, Issue 4, pp 623–631 | Cite as

HuR facilitates cancer stemness of lung cancer cells via regulating miR-873/CDK3 and miR-125a-3p/CDK3 axis

  • Yu Zhang
  • Limin Yang
  • Chunhua Ling
  • Wei Heng
Original Research Paper



To study the roles and mechanisms of HuR in cancer stem cell maintenance of lung cancer.


HuR expression was increased in tumor spheres of lung cancer cells. Knockdown of HuR suppressed spheroid formation and size, inhibited the expression of stemness-related marker, Oct4, Nanog and ALDH in lung cancer cells. Importantly, HuR and CDK3 expressions were increased in lung cancer tissues compared with normal adjacent tissues, and positively correlated. Mechanistically, HuR directly bound to CDK3, and increased CDK3 mRNA stability and expression. Additionally, miR-873 or miR-125a-3p attenuated the promotion of HuR on CDK3 expression and lung cancer stemness. Furthermore, HuR facilitated lung cancer stemness dependent on CDK3 expression. miR-873 or miR-125a-3p level was negatively correlated with HuR and CDK3 expression levels in lung cancer tissues.


HuR facilitates lung cancer stemness via regulating miR-873/CDK3 and miR-125a-3p/CDK3 axis.


CDK3 HuR Lung cancer miR-873 miR-125a-3p Stemness 


Supporting information

Supplementary Table 1—PCR primer sequences.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

Supplementary material

10529_2018_2512_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 12 kb)


  1. Blanco FF, Preet R, Aguado A, Vishwakarma V, Stevens LE, Vyas A, Padhye S, Xu L, Weir SJ, Anant S, Meisner-Kober N, Brody JR, Dixon DA (2016) Impact of HuR inhibition by the small molecule MS-444 on colorectal cancer cell tumorigenesis. Oncotarget 7:74043–74058PubMedPubMedCentralGoogle Scholar
  2. Butler SJ, Richardson L, Farias N, Morrison J, Coomber BL (2017) Characterization of cancer stem cell drug resistance in the human colorectal cancer cell lines HCT116 and SW480. Biochem Biophys Res Commun 490:29–35CrossRefPubMedGoogle Scholar
  3. Campbell TM, Main MJ, Fitzgerald EM (2013) Functional expression of the voltage-gated Na(+)-channel Nav1.7 is necessary for EGF-mediated invasion in human non-small cell lung cancer cells. J Cell Sci 126:4939–4949CrossRefPubMedGoogle Scholar
  4. Cui J, Yang Y, Li H, Leng Y, Qian K, Huang Q, Zhang C, Lu Z, Chen J, Sun T, Wu R, Sun Y, Song H, Wei X, Jing P, Yang X, Zhang C (2015) MiR-873 regulates ERalpha transcriptional activity and tamoxifen resistance via targeting CDK3 in breast cancer cells. Oncogene 34:4018CrossRefPubMedGoogle Scholar
  5. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270CrossRefPubMedPubMedCentralGoogle Scholar
  6. Kang F, Wang Z, Li G, Wang S, Liu D, Zhang M, Zhao M, Yang W, Wang J (2017) Inter-heterogeneity and intra-heterogeneity of alphavbeta3 in non-small cell lung cancer and small cell lung cancer patients as revealed by 68 Ga-RGD2 PET imaging. Eur J Nucl Med Mol Imaging 44:1520–1528CrossRefPubMedGoogle Scholar
  7. O’Day E, Le MT, Imai S, Tan SM, Kirchner R, Arthanari H, Hofmann O, Wagner G, Lieberman J (2015) An RNA-binding protein, Lin28, recognizes and remodels G-quartets in the MicroRNAs (miRNAs) and mRNAs it regulates. J Biol Chem 290:17909–17922CrossRefPubMedPubMedCentralGoogle Scholar
  8. Wang J, Li D, Wang B, Wu Y (2013) Predictive and prognostic significance of cytoplasmic expression of ELAV-like protein HuR in invasive breast cancer treated with neoadjuvant chemotherapy. Breast Cancer Res Treat 141:213–224CrossRefPubMedGoogle Scholar
  9. Won HY, Lee JY, Shin DH, Park JH, Nam JS, Kim HC, Kong G (2012) Loss of Mel-18 enhances breast cancer stem cell activity and tumorigenicity through activating notch signaling mediated by the Wnt/TCF pathway. FASEB J 26:5002–5013CrossRefPubMedGoogle Scholar
  10. Zhang W, Vreeland AC, Noy N (2016) RNA-binding protein HuR regulates nuclear import of protein. J Cell Sci 129:4025–4033PubMedPubMedCentralGoogle Scholar
  11. Zhang Z, Huang A, Zhang A, Zhou C (2017) HuR promotes breast cancer cell proliferation and survival via binding to CDK3 mRNA. Biomed Pharmacother 91:788–795CrossRefPubMedGoogle Scholar
  12. Zheng L, Meng X, Li X, Zhang Y, Li C, Xiang C, Xing Y, Xia Y, Xi T (2017) miR-125a-3p inhibits ERalpha transactivation and overrides tamoxifen resistance by targeting CDK3 in estrogen receptor-positive breast cancer. FASEB J. PubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Respiratory and Critical MedicineThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  2. 2.Department of Respiratory MedicineWuxi No.9 People’s Hospital affiliated to Soochow UniversityWuxiChina

Personalised recommendations