Tumor Biology

, Volume 35, Issue 1, pp 631–640 | Cite as

Upregulation of miR-136 in human non-small cell lung cancer cells promotes Erk1/2 activation by targeting PPP2R2A

  • Sining Shen
  • Han Yue
  • Yin Li
  • Jianjun Qin
  • Ke Li
  • Ying Liu
  • Jiaxiang Wang
Research Article

Abstract

MicroRNAs (miRNAs) have been integrated into cancer development and progression, because they repress translation of target genes which can be tumor suppressors and oncogenes. A number of miRNAs have been found to be closely related to human non-small cell lung cancer (NSCLC). However, the roles of miR-136 in NSCLC are still largely unknown. Here, we show that miR-136 is significantly upregulated in human NSCLC primary tumors and cell lines compared to their nontumor counterparts. Suppression of miR-136 expression in NSCLC cell line A549 inhibited both anchorage-dependent and anchorage-independent proliferation. Further studies showed that suppression of miR-136 expression attenuated phosphorylation of extracellular-signal-regulated kinase 1/2 (Erk1/2). We found that serine/threonine protein phosphatase 2A 55 kDa regulatory subunit B α isoform (PPP2R2A, also known as B55α) was a direct target of miR-136, and suppression of miR-136 expression led to a robust increase in both mRNA and protein levels of PPP2R2A. We found that miR-136 promoted phosphorylation of Erk1/2 through inhibition of PPP2R2A expression, and forced overexpression of PPP2R2A abrogated promotion of Erk1/2 phosphorylation by miR-136. Moreover, forced overexpression of PPP2R2A abrogated the promoting effect of miR-136 on cell growth and led to a reduced growth rate of NSCLC cells. Our findings indicate that miR-136 promotes Erk1/2 phosphorylation through targeting PPP2R2A in NSCLC cells and suggest that it may serve as a therapeutic target in NSCLC therapy.

Keywords

miR-136 Non-small cell lung cancer (NSCLC) Cell proliferation Extracellular-signal-regulated kinase 1/2 (Erk1/2) Serine/threonine protein phosphatase 2A 55 kDa regulatory subunit B α isoform (PPP2R2A) 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 91071909).

Conflicts of interest

None

Supplementary material

13277_2013_1087_Fig6_ESM.jpg (24 kb)
Supplemental Fig. 1

Typical amplification plot of the U6 RNA in 37 pairs of NSCLC tissues and matched nontumor tissues obtained using quantitative RT-PCR assay. Equal amounts of RNA were used for all the samples (JPEG 24 kb)

13277_2013_1087_MOESM1_ESM.tif (1.5 mb)
High resolution image (TIFF 1544 kb)
13277_2013_1087_Fig7_ESM.jpg (21 kb)
Supplemental Fig. 2

Typical amplification plot of the U6 RNA in NSCLC cell lines A549, SPC-A1, NCI-H1650, NCI-H1299 and the normal bronchial epithelial cell line 16HBE obtained using quantitative RT-PCR assay. Equal amounts of RNA were used for all the samples (JPEG 21 kb)

13277_2013_1087_MOESM2_ESM.tif (1.3 mb)
High resolution image (TIFF 1338 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Sining Shen
    • 1
    • 3
  • Han Yue
    • 2
  • Yin Li
    • 3
  • Jianjun Qin
    • 3
  • Ke Li
    • 4
  • Ying Liu
    • 4
  • Jiaxiang Wang
    • 1
  1. 1.Department of SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Department of OncologyThe First People’s Hospital of Zhengzhou CityZhengzhouChina
  3. 3.Department of Thoracic SurgeryAffiliated Tumor Hospital of Zhengzhou UniversityZhengzhouChina
  4. 4.Department of OncologyAffiliated Tumor Hospital of Zhengzhou UniversityZhengzhouChina

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