SIRT1 overexpression protects non-small cell lung cancer cells against osteopontin-induced epithelial-mesenchymal transition by suppressing NF-κB signaling

Abstract

Osteopontin (OPN) is a promoter for tumor progression. It has been reported to promote non-small cell lung cancer (NSCLC) progression via the activation of nuclear factor-κB (NF-κB) signaling. As the increased acetylation of NF-κB p65 is linked to NF-κB activation, the regulation of NF-κB p65 acetylation could be a potential treatment target for OPN-induced NSCLC progression. Sirtuin 1 (SIRT1) is a deacetylase, and the role of SIRT1 in tumor progression is still controversial. The effect and mechanism of SIRT1 on OPN-induced tumor progression remains unknown. The results presented in this research demonstrated that OPN inhibited SIRT1 expression and promoted NF-κB p65 acetylation in NSCLC cell lines (A549 and NCI-H358). In this article, overexpression of SIRT1 was induced by infection of SIRT1-overexpressing lentiviral vectors. The overexpression of SIRT1 protected NSCLC cells against OPN-induced NF-κB p65 acetylation and epithelial-mesenchymal transition (EMT), as indicated by the reduction of OPN-induced changes in the expression levels of EMT-related markers and cellular morphology. Furthermore, SIRT1 overexpression significantly attenuated OPN-induced cell proliferation, migration and invasion. Moreover, overexpression of SIRT1 inhibited OPN-induced NF-κB activation. As OPN induced NSCLC cell EMT through activation of NF-κB signaling, OPN-induced SIRT1 downregulation may play an important role in NSCLC cell EMT via NF-κB signaling. The results suggest that SIRT1 could be a tumor suppressor to attenuate OPN-induced NSCLC progression through the regulation of NF-κB signaling.

Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer

“…The analysis of OPN expression levels in 73 advanced NSCLC patients indicated that OPN overexpression was significantly associated with tumor differentiation ( P =0.031), metastasis status ( P =0.019), and the response to platinum-based chemotherapy ( P =0.038). Combined with the reports of Shojaei et al and Li et al, 35 , 36 OPN levels were correlated with the progression of NSCLC and the efficacy of platinum-based chemotherapy in patients with NSCLC. However, the underlying molecular phenomenon is rarely uncovered.…”

Hydrogen sulfide attenuates cigarette smoke-induced airway remodeling by upregulating SIRT1 signaling pathway

“…SIRT1 plays a crucial role in many pathophysiological processes, including oxidative stress, mitochondria dysfunction and EMT [9,10,13]. We then investigated the involvement of SIRT1 in the protective effect of NaHS on EMT in vivo and in vitro , by examining the SIRT1 levels after CS exposure in the mice and CSE stimulation in the 16HBE cells.…”

“…For instance, SIRT1 can regulate a stress-response transcription factor, FOXO3, thereby downregulating oxidative stress [[10], [11], [12]]. SIRT1 also regulates the RelA/p65 subunit of NF-kB, thereby protecting non-small cell lung cancer cells against osteopontin-induced EMT [13]. Rajendrasozhan and others have shown that SIRT1 is reduced in the lungs of smokers and patients with COPD [14,15], and activation of SIRT1 by SRT1720 protected against CS-induced emphysema in mice [10].…”

Thrombin is a therapeutic target for non-small-cell lung cancer to inhibit vasculogenic mimicry formation

“…Studies have shown that NF-κB plays an important role in the EMT process during liver fibrogenesis 35 and EMT of NSCLC cells occurs via NF-κB activation. 36 Tian et al 37 reported that NF-κB is a master regulator of EMT autocrine loops. We also found that pyrrolidinedithiocarbamate ammonium (PDTC), an inhibitor of NF-κB, could inhibit thrombin-induced increased expression of snail and N-cadherin and inhibit thrombin-induced decreased expression of E-cadherin.…”