Inhibition of SENP1 induces radiosensitization in lung cancer cells

Abstract

Lung cancer is one of the most common and lethal types of malignancy. To date, radiotherapy and chemotherapy have been used as the two major treatment methods. However, radioresistance of lung cancer remains a therapeutic hindrance. The aim of this study was to identify whether small ubiquitin-related modifier (SUMO)-specific protease 1 (SENP1) is a marker of radioresistance that may serve as a target for enhancing the efficacy of lung carcinoma radiotherapy. SENP1 was observed to be overexpressed in lung cancer tissues, and the modulation of SENP1 expression was demonstrated to significantly affect the proliferation of lung cancer cells. Moreover, silencing the expression of SENP1 using small interfering RNA (siRNA) significantly sensitized lung cancer cells to radiation. Mechanically, it was demonstrated that SENP1 depletion significantly enhanced ionizing radiation (IR)-induced cell cycle arrest, γ-H2AX expression and apoptosis. Thus, these data suggest that SENP1 may be a desirable drug target for lung carcinoma radiotherapy.

The Ubiquitin-Like SUMO System and Heart Function

“…SENP1 acts also as a factor to develop tolerance to hypoxia, contributing to hypoxia-driven vascular endothelial growth factor expression and angiogenesis in endothelial cells, 154,155 and protects against hydrogen peroxide-induced cell death, whereas its depletion enhances apoptosis in vitro. 156,157 It is, therefore, obvious that the simple model of a beneficial role of enhanced SUMOylation Figure 2. Effect of differential SUMOylation of dynaminrelated protein (Drp1) on apoptotic cell death in various cell types.…”

Deficiency of SUMO-specific protease 1 induces arsenic trioxide-mediated apoptosis by regulating XBP1 activity in human acute promyelocytic leukemia

“…However, knockdown of SENP1 had no effect on the SUMOylation of PML-RARα in NB4 cells, even after NB4 cells were treated with 1 µΜ As 2 O 3 (data not shown), suggesting the possibility that other members of the SENP family may be involved in regulating the level of SUMOylated PML-RARα, which remains to be further investigated. It has been reported that knockdown of SENP1 could promote drug-induced cell apoptosis in MEF and HEK 293T cells, as well as lung cancer and Burkitt lymphoma cells (17–19). However, our results revealed that downregulation of SENP1 had no effect on the spontaneous apoptosis or differentiation of NB4 cells (Fig.…”

“…Numerous studies have demonstrated that SENP1 is overexpressed and contributes significantly to the development and progression of tumors, including prostatic intraepithelial neoplasia, colon cancer and pancreatic cancer (14–16). Previous studies have revealed that deficiency or downregulation of SENP1 could induce radiosensitization in lung cancer cells (17), promote endoplasmic reticulum (ER) stress-induced apoptosis in MEF and HEK 293T cells (18), and increase apoptosis in Burkitt lymphoma cells (19). Furthermore, SENP1 is also involved in the formation of PML protein nuclear bodies (20,21), which were originally characterized as part of a fusion protein with PML-RARα in patients with APL (22).…”

Small ubiquitin‐like modifier/sentrin‐specific peptidase 1 associates with chemotherapy and is a risk factor for poor prognosis of non‐small cell lung cancer

“…The overexpression of SENP1 contributes to the abnormity of the cell nucleus and mitochondria . It has been reported that the expression of SENP1 was upregulated in NSCLC …”

“…Vascular endothelial growth factor (VEGF) is a target of HIF‐1α, and the activation of HIF‐1α/VEGF signaling pathway is essential for angiogenesis, tumor angiogenesis, atherosclerosis, and diabetes mellitus . In contrast, the suppression of SENP1, HIF‐1α, and VEGF was reported to suppress tumor development and aggressiveness of cancers, including NSCLC . However, there was less information on the in vivo association of SENP1 expression with chemotherapy resistance of NSCLC.…”