bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2019‒05‒12
two papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge

  1. Mol Med Rep. 2019 Apr 16.
    Li Y, Zhao L, Qi Y, Yang X.
      Previous reports have indicated a potential link between microRNA (miR)‑214 and hypoxia. In the present study, the biological functions and potential mechanisms of miR‑214 were determined, as well as its correlation with HIF‑1α signaling in non‑small cell lung cancer (NSCLC) cells. Quantitative polymerase chain reaction revealed that miR‑214 expression was upregulated in lung cancer tissues compared with adjacent normal tissues. miR‑214 mimics were transfected into A549 cells, and MTT, colony formation, invasion and wound healing assays were performed. It was demonstrated that miR‑214 mimic transfection promoted the invasion, proliferation and migration of A549 cells. Furthermore, miR‑214 inhibitor transfection decreased H1299 cell invasion, proliferation and migration. Next, the association between miR‑214 expression and the HIF‑1α signaling cascade was examined. It was demonstrated that miR‑214 mimics upregulated the expression of hypoxia‑inducible factor (HIF)‑1α, vascular endothelial growth factor (VEGF), adenylate kinase 3 and matrix metalloproteinase (MMP)2, whereas miR‑214 inhibitor downregulated the expression of these factors. Using prediction software, it was demonstrated that tumor suppressor ING4 was a target of miR‑214. A luciferase reporter assay confirmed that ING4 was a direct target of miR‑214. There was a negative correlation between ING4 and miR‑214 expression in lung cancer tissues. In addition, ING4 siRNA and plasmid was transfected into cells in order to validate its effect on HIF‑1α, MMP2 and VEGF expression. ING4 overexpression downregulated HIF‑1α and its targets MMP2 and VEGF, while ING4 siRNA upregulated HIF‑1α, MMP2 and VEGF. In conclusion, it was demonstrated that miR‑214 targeted ING4 in lung cancer cells, and upregulated the HIF‑1α cascade, leading to MMP2 and VEGF upregulation. This approach may help to clarify the role of miRNA in non‑small lung cancer and may be a new therapeutic target for non‑small lung cancer.
  2. Eur J Pharmacol. 2019 May 03. pii: S0014-2999(19)30303-6. [Epub ahead of print]
    Rajavel T, Priya GB, Suryanarayanan V, Singh SK, Devi KP.
      Daucosterol (DS) is a plant phytosterol which is shown to induce oxidative stress mediated apoptosis in various cancer cell lines. However, the molecular mechanism underlying its cellular action has not been documented against Non- Small Cell Lung Cancer (NSCLC). Therefore, we attempted to decipher the mechanisms responsible for DS-induced anti-proliferation on human NSCLC cells. The present study showed, DS strongly inhibits the growth of A549 cells after 72 h time point with an IC50 value of ∼20.9 μM. Further DS elicits increased reactive oxygen species level and promote intrinsic apoptotic cell death on A549 cells as evidenced by increased expression of caspase-3, caspase-9, Bax, PARP inactivation, cytochrome-c release, and diminished expression of bcl-2 protein. DS failed to display its apoptotic actions upon pretreatment with the reactive oxygen species inhibitor NAC (N-acetyl cysteine). Indeed, apoptotic signal which was enhanced through p53/p21 activation and knockdown of p53 expression also moderately affected the DS induced apoptosis. In addition, DS preferentially inhibited the cell growth of p53 wild-type NSCLC cell lines than the mutant p53 models. Further, we show that inhibition of Thioredoxin (TrxR) redox system is principally associated with DS induced oxidative stress mediated apoptotic cell death on A549 cells. Moreover, we also demonstrated that DS stably interacted with serine residues in TrxR active sites. The obtained results confirmed that the anti-proliferative mechanism and increased reactive oxygen species level of DS was associated with down-regulation of TrxR1 pathway which triggers the p53 mediated intrinsic apoptotic mode of cell death in NSCLC cells.
    Keywords:  Apoptosis; Daucosterol; Lung cancer; Reactive oxygen species; Thioredoxin redox system