Proteinase-activated receptor-2 enhances Bcl2-like protein-12 expression in lung cancer cells to suppress p53 expression

Abstract

IntroductionThe pathogenesis of lung cancer is unclear. Less expression of p53 or p53 mutation was identified in lung cancer cells, which plays a role in the development of lung cancer. Recent reports indicate that Bcl2-like protein-12 (Bcl2L12) can inhibit the expression of p53. Lung cancer cells express proteinase-activated receptor-2 (PAR2). This study tests the hypothesis that activation of PAR2 inhibits the expression of p53 in lung cancer cells.Material and methodsLung cancer cells were collected from patients with non-small cell lung cancer (NSCLC). The cells were exposed to active peptides or trypsin in the culture for 48 h. The expression of p53 was assessed by RT-qPCR and Western blotting.ResultsWe observed that lung cancer cells express Bcl2L12. Activation of PAR2 increases expression of Bcl2L12 in lung cancer cells. Bcl2L12 mediates PAR2-suppressed p53 expression in lung cancer cells. IgE-activated mast cell suppression of p53 expression in lung cancer cells can be prevented by knocking down Bcl2L12. The Bcl2L12 bound Mdm2, the transcription factor of p53, to prevent the Mdm2 from binding to the promoter of p53 and thus inhibited p53 expression in lung cancer cells. PAR2 could attenuate lung cancer cell apoptosis via inducing Bcl2L12.ConclusionsLung cancer cells express Bcl2L12, which mediates the effects of activation of PAR2 on suppressing the expression of p53 in lung cancer cells, implying that Bcl2L12 may be a novel therapeutic target for the treatment of lung cancer.

Treatment of Pulpectomized Teeth With Trypsin Prior to Transplantation of Mobilized Dental Pulp Stem Cells Enhances Pulp Regeneration in Aged Dogs

“…Therefore, it is important to stimulate anti-apoptosis factors in the aged cells. Activation of PAR2 could increase MCL-1, an anti-apoptotic Bcl-2 family member (Iablokov et al, 2014) and Bcl-2 like protein 12 expression (Ma et al, 2019). In consistent, our results showed that trypsin activated aged PDLCs to release more PAR2 compared to young PDLCs and stimulated expression of the anti-apoptotic factor Bcl2 in the aged PDLCs but not in the young PDLCs.…”

Systemic Inflammation and Activation of Haemostasis Predict Poor Prognosis and Response to Chemotherapy in Patients with Advanced Lung Cancer

“…Increased coagulation and inflammation seem to be associated with increased tumour aggressiveness, as characterized by shorter survival times and worse response to systemic anticancer therapy. Results of experimental and translational work suggest an underlying causal relationship by linking tumour-induced inflammation and hypercoagulability to cellular pathways and alterations in the tumour microenvironment that support proliferation, invasion, metastasis and the evasion of apoptotic mechanisms [6,7,[13][14][15]18,19]. These findings are strongly supported by our observations that add a valuable clinical perspective to our understanding of the complex interplay of inflammation, haemostasis and lung cancer.…”

“…Interestingly, also the haemostatic system has been suggested to support a tumour-promoting microenvironment in lung cancer. For instance, the expression of tissue factor and proteinase-activated receptors in lung cancer have been linked to impaired apoptosis on a cellular level, worse survival and the metastatic process [13][14][15][16][17]. Further, the haemostatic system has been demonstrated to be involved in angiogenesis, tumour growth and metastatic spread in experimental models of lung cancer [18,19].…”

Investigation the Role of Autophagy in Non-Small Cell Lung Cancer

“…According to the data obtained, the overexpression of these markers was found in NSCLC patients compared to normal samples. In recent studies, overexpression of bcl2 was observed in lung cancer cells (Ma et al, 2019). In other study showed that bcl2 expression and bcl2/ Bax expression level might be beneficial as independent diagnostic factors in lung carcinoids.…”