DDIT4在皮肤基底细胞癌中的表达及对细胞增殖和自噬通路的调控

DDIT4 expression in cutaneous basal cell carcinoma and its regulation on cell proliferation and autophagy flux

目的:检测DNA损伤诱导转录因子-4(DNA damage-inducible transcript 4,DDIT4)在皮肤基底细胞癌(basal cell carcinoma,BCC)中的表达及其对下游的细胞蛋白合成、增殖和自噬水平的影响。方法:采用免疫组化和Western blot分别对15例人皮肤BCC组织和正常皮肤15例进行检测,比较两者DDIT4、p S6K1、p4E-BP1和LC3Ⅱ/Ⅰ的表达。结果:与正常组织相比,DDIT4(0.247±0.152,P=0.005)在BCC中的表达被明显抑制,伴p4E-BP1表达(0.290±0.169,P=0.015)和LC3Ⅱ/Ⅰ的比值(0.692±0.154,P=0.007)降低,但p S6K1(0.837±0.050,P=0.000)表达明显增加,具有统计差异。结论:DDIT4在BCC中的表达受抑制,可能通过其下游的mTORC1通路进而促进癌细胞的蛋白合成和增殖能力,但自噬流受阻,参与BCC的发生发展过程;DDIT4及其下游通路信号可能作为BCC的进一步治疗及预后研究的靶点。

Objective:To explore the expression of DDIT4(DNA damage-inducible transcript 4)in human cutaneous basal cell carcinoma(BCC)tissues and its regulating effects on cellular protein synthesis,proliferation and autophagy flux of the downstream signals involved in. Methods:Immunohistochemistry and Western blot were used to detect the expressions of DDIT4,pS6 K1,p4 E-BP1 and LC3 Ⅱ/Ⅰ in 15 cases of human skin BCC and 15 cases of normal skin tissues respectively. Results:The expression of DDIT4(0.247±0.152,P=0.005)in BCC was significantly inhibited as compared with that in the normal tissues. Meanwhile the expression of p4 E-BP1(0.290±0.169,P=0.015)and ratio of LC3 Ⅱ/Ⅰ(0.692±0.154,P=0.007)were decreased,but the expression of pS6 K1(0.837±0.050,P=0.000)was significantly increased. Conclusion:DDIT4 expression is inhibited in human BCC cells,which may promote the downstream protein synthesis and proliferation,and inhibit the autophagy flux through the mTORC1 pathway to finally involve in the pathogenesis and development of BCC. DDIT4 and its downstream signals may serve as target for the further treatment and prognosis of BCC.