Relationships Between Transcription Factor HMBOX1 And The Occurrence And Development Of High-grade Serous Ovarian Cancer

ObjectsOvarian cancer is one of the most common types of malignant tumors of female genital organs.Due to lacking of effective methods for early diagnosis and its widespread intraperitoneal metastasis,its mortality rate is still the highest in gynecological cancers,and the 5 year survival rate is poor after diagnosis.According to the histological characteristics,epithelial ovarian cancer(EOC)can be mainly divided into the following subtypes:serous,endometrioid,mucinous,clear cell and transitional cell.In these subtypes,serous tumors are the most common ones.High-grade serous ovarian carcinoma(HGSOC)is a distinct histological subtype of EOC.Although it has been normally proposed that the origin of ovarian cancer is ovarian surface epithelium,recent researches have brought a persuasive hypothesis that HGSOC may arise from distant fallopian tube epithelium.Because of the high mortality and the complex pathogenesis of HGSOC,to clarify the mechanism of the occurrence and development of HGSOC and to hunt for new therapeutic targets have become a valuable and essential task in gynecologic oncology research.Homeobox-containing genes play an important role in the regulation of embryonic development and cell proliferation.In recent years,it is found that some homeobox genes,as transcription regulatory factors,are also involved in the occurrence and progression of many tumors.Currently,the relationship between hepatocyte nuclear factor(HNF)subfamily genes and cancers has gradually abstracted the attention.Homeobox-containing 1(HMBOX1)is a member of the HNF subfamily of the homeobox genes.It is highly conserved,and it has high homology with HNF.It is reported that HMBOX1 is widely expressed in at least 18 human tissues.It is found that the high expression of HMBOX1 could inhibit the killing activity of NK cells via NKG2D/DAP10 signaling pathway.It is reported that HMBOX1 may play a key role in regulating the differentiation of bone marrow stromal cells into vascular endothelial cells.Researches have reported that HMBOX1 may be correlated with tumorigenesis,but whether HMBOX1 is related to the regulation of ovarian cancer has not been reported.Here we aimed to reveal the expression of HMBOX1 in HGSOC,and to investigate whether there exist some relationships between the different expression of HMBOX1 in EOC cell lines and the cell biological behaviors,this may lay groundwork for our further study to explore the function of HMBOX1 and its relationship with the occurrence and development of ovarian cancer.Methods1.Real-time quantitative RT-PCR,Western blot analysis and immunohistochemical staining was used to detect and compare HMBOX1 expression in normal ovarian surface epithelium(OSE),fallopian tube epithelium(FTE),serous borderline ovarian tumor(SBT)and HGSOC tissues,together with one human normal ovarian surface epithelial cell line(HOSEpiC)and 3 EOC cell lines(HO8910,A2780 and SKOV3).2.To measured cell proliferation,MTT assay was performed.Colony formation assay was used for detecting colony-forming ability.For cell invasion and migration analysis,Matrigel-coated transwell assay and wound healing assay were performed respectively.Flow cytometry was used for cell cycle analysis.3.qRT-PCR was used to detect several genes involved in cell cycle progression.Results1.HMBOX1 expression was decreased in HGSOC tissues compared with OSE tissues.Compared with HOSEpiC,HMBOX1 expression was decreased in HO8910 and A2780 cell lines.2.By observing cell biological behaviors,we found that there existed some relationships between the expression of HMBOX1 and cell proliferation.And there is no relationship between the expression of HMBOX1 and cell migration or cell invasion.3.HMBOX1 may probably be associated with certain signaling molecules such as cyclin D1 and cyclin E1 in cell cycle regulation.ConclusionHMBOX1 may be related to the EOC cell proliferation and the molecular mechanisms of the development in HGSOC.