Tumor Biology

, Volume 37, Issue 1, pp 291–298 | Cite as

MicroRNA-138 negatively regulates non-small cell lung cancer cells through the interaction with cyclin D3

  • Li-ping Han
  • Tian Fu
  • Yong Lin
  • Jian-Long Miao
  • Qiu-Fang Jiang
Research Article


Previous studies demonstrate that microRNA-138 (miR-138) is critical in non-small cell lung cancer (NSCLC) regulation. We further explored the molecular mechanism of miR-138 in NSCLC. Lentivirus was used to upregulate miR-138 in NSCLC cell lines H460 and SPC-A1 cells. Previously known effects of miR-138 upregulation on NSCLC, proliferation, cell cycle division, and cisplatin sensitivity were examined in H460 and SPC-A1 cells. Moreover, previously unknown effect of miR-138 upregulation on NSCLC migration was also examined in H460 and SPC-A1 cells. A new miR-138 downstream target, cyclin D3 (CCND3), was assessed by dual-luciferase reporter assay and quantitative real-time PCR (qRT-PCR). CCND3 was then ectopically overexpressed in H460 and SPC-A1 cells. The effects of forced overexpression of CCND3 on miR-138-induced NSCLC regulations were further examined by proliferation, cell cycle, cisplatin sensitivity, and migration assays, respectively. Lentivirus-induced miR-138 upregulation inhibited NSCLC proliferation and cell cycle division, in line with previous findings. Moreover, we found that miR-138 upregulation had other anti-tumor effects, such as increasing cisplatin sensitivity and reducing cancer migration, in H460 and SPC-A1 cells. Luciferase assay and qRT-PCR showed that CCND3 was directly targeted by miR-138. Forced overexpression of CCND3 in H460 and SPC-A1 cells reversed the anti-tumor effects of miR-138 upregulation on cancer cell growth, cell cycle, cisplatin sensitivity, and migration. Our study revealed novel anti-cancer effects of miR-138 upregulation in NSCLC, as well as its new molecular target of CCND3.


NSCLC miR-138 CCND3 Cisplatin 


Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Li-ping Han
    • 1
  • Tian Fu
    • 1
  • Yong Lin
    • 1
  • Jian-Long Miao
    • 1
  • Qiu-Fang Jiang
    • 1
  1. 1.Department of Respiratory MedicineJining First People’s HospitalJiningChina

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