SIRT3 is correlated with the malignancy of non-small cell lung cancer

Abstract

The mitochondrial deacetylase SIRT3 plays a pivotal role in the initiation and the progression of certain cancers acting as an oncogene. However, in others it acts anti-oncogenically. Its conflicting action is possibly due to the different key proteins it modifies depending on the context of active intracellular signaling pathways in different cancers. SIRT3 is thus a novel target for preventing and treating cancer. In the present study, we explored the function of SIRT3 in non-small cell lung cancer (NSCLC) with the aim of elucidating the underlying mechanisms. We first determined the SIRT3 expression levels by real-time PCR, western blotting and immunohistochemistry on tissue microarrays of paired samples of NSCLC tissue and adjacent normal tissue from 70 patients with associated clinicopathological data. Levels of SIRT3 protein and mRNA were significantly increased in NSCLC tissue, compared with normal tissue (P<0.05). Expression of SIRT3 in NSCLC positively correlated with that of malignant biomarker Ki-67 (P<0.05) and oncogene p-Akt (P<0.05). Patients with higher SIRT3 expression had a shorter overall survival duration (P<0.05). NSCLC tissue of squamous cell carcinoma type had higher SIRT3 expression compared with other types (P<0.05). Furthermore, among the clinicopathological variables examined, SIRT3 expression was correlated only with pathological type (P<0.05). In NSCLC cell lines, we found that downregulation of SIRT3 by siRNA decreased the activation of Akt, and that SIRT3 overexpression caused the activation of Akt. In addition, in a NSCLC cell line, SIRT3 was able to co-immunoprecipitate Akt and co-located with Akt, suggesting that SIRT3 regulates the activation of Akt through post-transcriptional modification. Our findings suggest that SIRT3 promotes the malignancy of NSCLC, showing an oncogenic preference towards squamous cell carcinoma, and that could represent a novel target for treatment.

<p>Aberrantly High Expression Of NOK/STYK1 Is Tightly Associated With The Activation Of The AKT/GSK3β/N-Cadherin Pathway In Non-Small Cell Lung Cancer</p>

“…Pannoramic 250/ MIDI (3DHISTECH) was used to scan and digitalize the slides. Pannoramic Viewer v. 2.0 and NuclearQuant application for PV v.2.0.0.46136, both of which are manufactured by 3DHISTECH, were used to analyze the slides 30. …”

Sirt3 deficiency impairs neurovascular recovery in ischemic stroke

“…Moreover, the role and putative mechanism of Sirt3 in chronic stroke are also unknown. Previous studies have shown that downregulation of Sirt3 decreased the activation of AKT which is involved in neurogenesis and angiogenesis, and Sirt3 is essential for apelin‐mediated angiogenesis in postmyocardial infarction of diabetes . Rehabilitation after ischemic stroke requires the recovery of neural, vascular, and connective tissue components in the damaged brain region; our previous study showed that Sirt3 could mediate the inhibitory effect of adjudin on glial scar formation which was correlated with neural functional recovery following ischemic stroke .…”

Nicotinic-nAChR signaling mediates drug resistance in lung cancer

“…Nicotine-mediated cancer progression is mediated by nicotine/nAChRs signaling. By contrast to the tumor-suppressing role of SIRT2/4, the roles of SIRT1/6/7 and mitochondrial SIRT3/5 are strongly associated with drug resistance in lung cancer [119,120,124,135,142,144,146,[150][151][152][153][154]. However, SIRT1/2 inhibitor, sirtinol, can increase anticancer potential and chemosensitivity in several cancer cells [102,160,161].…”

“…SIRT3, located in mitochondria, is correlated with NSCLC malignancy [142]. α7nAChRs activation inhibits platelet-derived growth factor-induced cells migration by activating the mitochondrial deacetylase SIRT3, implying a critical role for α7nAChRs in mitochondrial biology and PDGF-related diseases [143].…”

“…The activity of SIRT3 can protect cancer cells from chemotherapy-induced oxidative stress [144,145]. Additionally, SIRT3 promotes the activation of AKT signaling pathways in NSCLC [142]. SIRT3 promoted p53 degradation in PTEN-deficient NSCLC cell lines via the ubiquitin-proteasome pathway [146].…”