Noxin promotes proliferation of breast cancer cells via P38-ATF2 signaling pathway

Abstract

Noxin (also called chromosome 11 open reading frame 82 or DNA damage-induced apoptosis suppressor) is associated with anti-apoptosis and cell proliferation in response to stress signals. However, to our knowledge, the role of Noxin in regulating cell proliferation is still controversial and there are no reports of the function and clinicopathological association in breast cancer. In this study, immunohistochemistry results showed that Noxin expression was significantly correlated with advanced tumor-node-metastasis stage (p = 0.027), positive regional lymph node metastasis (p = 0.002), and poor overall survival (p = 0.002). Proliferation assay results showed that Noxin obviously promoted the ability of proliferation of normal breast cells. Subsequent western blot results revealed that Cyclin D1 and Cyclin E1 were upregulated by overexpressing Noxin, whereas Cyclin D1 and Cyclin E1 were downregulated after depleting Noxin. The levels of phosphorylated P38 and activating transcription factor 2 were obviously increased after overexpressing Noxin, and their expression was downregulated accordingly by transfecting Noxin-small interfering RNA. Moreover, P38 inhibitor counteracted the elevating expression of phosphorylated activating transcription factor 2, Cyclin D1, and Cyclin E1 induced by Noxin overexpression and thereby reversed the effect of Noxin overexpression on facilitating cell growth. Taken together, our studies indicated that Noxin was overexpressed in breast cancer and its positive expression was significantly correlated with advance tumor-node-metastasis stage, positive lymph node metastasis, and poor prognosis. Noxin facilitated the expression of Cyclin D1 and Cyclin E1 through activating P38-activating transcription factor 2 signaling pathway, thus enhanced cell growth of breast cancer.

TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non‐small cell lung cancer patients

“…Our studies suggested that TIMM50 also promoted tumor proliferation and invasion in NSCLC cells via upregulating Cyclin D1 and Snail and downregulating E‐cadherin. During tumor progression, multiple signaling pathways, such as ERK, AKT, P38, and FAK, were involved in modulating the expression of Cyclin D1, Snail, and E‐cadherin . Using Western blotting analysis, we found that overexpression of TIMM50 was capable of upregulating the levels of phosphorylated ERK and P90RSK.…”

“…During tumor progression, multiple signaling pathways, such as ERK, AKT, P38, and FAK, were involved in modulating the expression of Cyclin D1, Snail, and E-cadherin. [14][15][16][17][18][19][20][21] Using Western blotting analysis, we found that overexpression of TIMM50 was capable of upregulating the levels of phosphorylated ERK and P90RSK. To further test the effect induced by overexpressing TIMM50 was mediated by activating ERK signaling pathway.…”

FAM98A promotes proliferation of non-small cell lung cancer cells via the P38-ATF2 signaling pathway

“… 20 These data were consistent with previously published reports that the P38-ATF2 signaling pathway promotes proliferation via transcriptional activation of key cell-cycle regulators. 21 – 23 A previous report showed that FAM98A, as a novel substrate of PRMT1, is arginine-methylated by PRMT1. 6 PRMT1 is associated with p38α in cells, as shown by co-immunoprecipitation, and directly methylates p38α in in vitro methylation assays.…”

Sevoflurane suppresses proliferation by upregulating microRNA-203 in breast cancer cells

“…For mRNA RT-qPCR, cDNA was reverse-transcribed from mRNA by M-MLV Reverse Transcriptase (Takara) using random primers and oligo (dT) primers. The quantification of level of target gene expression (2 -ΔΔCt ) was normalized to the endogenous GAPDH mRNA (7,22). The reaction conditions of PCR were according to the SYBR-Green qPCR Mix instruction (Bio-Rad Laboratories, Inc., Hercules, CA, USA).…”