BMC Cancer (Mar 2019)

MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway

  • Lin Lu,
  • Qiyao Liu,
  • Peipei Wang,
  • Yong Wu,
  • Xia Liu,
  • Chengyin Weng,
  • Xisheng Fang,
  • Baoxiu Li,
  • Xiaofei Cao,
  • Haibo Mao,
  • Lina Wang,
  • Mingmei Guan,
  • Wei Wang,
  • Guolong Liu

DOI
https://doi.org/10.1186/s12885-019-5400-3
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 11

Abstract

Read online

Abstract Background MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of miR-148b in regulating tumor progression remain unclear. Methods Firstly animal experiments were performed to verify whether miR-148b could inhibit the tumor growth. Then, the underlying mechanisms were studied by transfecting recombinant plasmids containing a miR-148b mimic or a negative control (NC) mimic (shRNA control) into NSCLC cell lines PC14/B and A549 cells. Tumor cells transfected with unpackaged lentiviral vectors was used as blank control. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. Cell cycle arrest was compared to clarify the mechanism underlying the tumor cell proliferation. Annexin V-FITC Apoptosis Detection kit was applied to investigate the effect of miR-148b on cell apoptosis. Furthermore, western blot analysis were performed to study the targeting pathway. Results We found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiment showed that miR-148b inhibited tumor cell proliferation. Besides, over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing NSCLC cells from entering the mitotic phase and enhanced tumor cell apoptosis. Further western blot analysis indicated that miR148b could inhibit mitogen-activated protein kinase/Jun N-terminal kinase (MAPK/JNK) signaling by decreasing the expression of phosphorylated (p) JNK. Conclusions These results demonstrate that miR-148b could inhibit the tumor growth and act as tumor suppressor by inhibiting the proliferation and inducing apoptosis of NSCLC cells by blocking the MAPK/JNK pathway.

Keywords