search button
Open Access

miR129‑1 regulates protein phosphatase 1D protein expression under hypoxic conditions in non‑small cell lung cancer cells harboring a TP53 mutation

  • Authors:
    • Hong‑Lei Yin
    • Hong‑Wei Xu
    • Qing‑Yan Lin

  • View Affiliations

  • Published online on: June 26, 2020     https://doi.org/10.3892/ol.2020.11783
  • Pages: 2239-2247

  • Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Protein phosphatase 1D (PPM1D), which functions as an oncogene, is a known target of the tumor suppressor p53 and is involved in p53‑regulated genomic surveillance mechanisms. PPM1D dephosphorylates both p53 and its ubiquitin ligase mouse double minute 2 homolog, as well as the RNA‑binding protein (RBM)38, which turns RBM38 from an inducer to inhibitor of TP53 translation. In addition, RBM38 induces PPM1D translation. Hence, the PPM1D‑RBM38‑p53 axis is important in maintaining genomic integrity and is often altered during tumorigenesis. TP53, which encodes p53, is deleted or mutated in >50% of cancer types, including lung cancer. Mutant p53 has been revealed to complex with hypoxia‑inducible factor 1α (HIF1α) and upregulate transcription of pro‑metastatic genes. However, the mechanism underlying the action of the PPM1D‑RBM38‑p53 axis in the context of mutant p53 under normoxic and hypoxic conditions is yet to be elucidated. In the present study, using non‑small cell lung cancer (NSCLC) cell lines harboring wild‑type (A549 cells) or hot‑spot mutant (NCI‑H1770 and R249WΔ‑TP53‑A549 cells) TP53, it was demonstrated that in cells harboring mutant p53, RBM38 was not the primary regulator of PPM1D translation under hypoxic conditions. Knockdown of RBM38 in TP53 mutant cells did not affect the PPM1D protein expression under hypoxic conditions. Instead, in NCI‑H1770 cells maintained under normoxic conditions, PPM1D was revealed as a target of micro RNA (miR)‑129‑1‑3p, a known tumor suppressor in lung cancer. Hypoxia resulted in the downregulation of miR‑129‑1‑3p expression, and thus, in the downregulation of PPM1D messenger RNA (mRNA) translation. In NCI‑H1770 cells grown under hypoxic conditions, the transient transfection of miR‑129‑1‑3p mimic, and not control mimic, repressed the expression of a reporter containing wild‑type, but not miR‑129‑1‑3p binding mutant, of the PPM1D 3'‑untranslated region (UTR). Analysis of NSCLC cell lines from the Broad Institute Cancer Cell Encyclopedia and patients with NSCLC from The Cancer Genome Atlas dataset revealed significant co‑occurrence of PPM1D/RBM38 and PPM1D/HIF1A mutations. However, there was no significant difference in the overall survival of patients with NSCLC with or without genomic alterations in TP53, RBM38, PPM1D and HIF1A. In summary, the current study demonstrated hypoxia‑dependent miR‑129‑1‑3p‑mediated regulation of PPM1D protein expression in NSCLC cell line harboring mutant TP53.
View Figures
View References

Related Articles

Journal Cover

September-2020
Volume 20 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

  • Journal Metrics
  • Impact Factor: 2.5
  • Ranked Oncology
    (total number of cites)
  • CiteScore: 5.7
  • CiteScore Rank: Q2: #139/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.574
  • SCImago Journal Rank (SJR): 0.644
International Symposium on Molecular Medicine Conference Banner
The Cancer Story
World Congress on Advances in Oncology and International Symposium on Molecular Medicine Conference Banner
World Academy Of Sciences Banner
Heyday Road Banner

0

Copy and paste a formatted citation
x
Spandidos Publications style
Yin HL, Xu HW and Lin QY: miR129‑1 regulates protein phosphatase 1D protein expression under hypoxic conditions in non‑small cell lung cancer cells harboring a TP53 mutation. Oncol Lett 20: 2239-2247, 2020.
APA
Yin, H., Xu, H., & Lin, Q. (2020). miR129‑1 regulates protein phosphatase 1D protein expression under hypoxic conditions in non‑small cell lung cancer cells harboring a TP53 mutation. Oncology Letters, 20, 2239-2247. https://doi.org/10.3892/ol.2020.11783
MLA
Yin, H., Xu, H., Lin, Q."miR129‑1 regulates protein phosphatase 1D protein expression under hypoxic conditions in non‑small cell lung cancer cells harboring a TP53 mutation". Oncology Letters 20.3 (2020): 2239-2247.
Chicago
Yin, H., Xu, H., Lin, Q."miR129‑1 regulates protein phosphatase 1D protein expression under hypoxic conditions in non‑small cell lung cancer cells harboring a TP53 mutation". Oncology Letters 20, no. 3 (2020): 2239-2247. https://doi.org/10.3892/ol.2020.11783