title: BMI-1 activation is crucial in hTERT-induced epithelial-mesenchymal transition of oral epithelial cells.
abstract: BMI-1 (B lymphoma Mo-MLV insertion region 1 homolog) has been reported to be over-expressed in cell immortalisation and the epithelial-mesenchymal transition (EMT) of cancer cells. The aim of this study is to study the roles of BMI-1 in the human telomerase reverse transcriptase (hTERT)-induced immortalisation and EMT. In this study, hTERT(+)-OME cells and hTERT(+)-HaCaT cells were acquired by viral transduction of hTERT to primary cultured oral keratinocytes and HaCaT cells (skin epidermal cells). siRNA transduction was used for the inhibition of BMI-1 expression. RT-PCR and Western blots were performed to detect the expressions of twist, vimentin, BMI-1, hTERT and p16INK4a in these cell lines. EMT was assessed by immunohistochemistry (expressions of cytokertin & vimentin), Western blots (expressions of Twist, vimentin & E-cadherin) and RT-PCR (expression of Twist). The results indicated that hTERT(+)-OME cells and hTERT(+)-HaCaT cells underwent EMT spontaneously with high expression of Twist. p16INK4a was silenced in both hTERT-transduced cells but could be detected in HaCaT cells. Moreover, BMI-1 was highly expressed in hTERT(+)-OME and hTERT(+)-HaCaT cells but was negative in HaCaT cells. When the expression of BMI-1 was blocked by siRNA transduction, the proliferations of hTERT(+)-OME and hTERT(+)-HaCaT cells were inhibited and the mono-spheroid colony formation of these hTERT-transduced cells was decreased. In addition, the expression of p16INK4a was regained while the expressions of EMT markers (twist and vimentin) were down-regulated in these two BMI-1 blocking cell lines. To conclude, this study suggests BMI-1 expression plays a role in hTERT-induced immortalisation and EMT.
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qiao
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Chen
authors.forename: Fengchun
authors.initials: F
authors.lastname: Hu
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
authors.forename: Alfred K
authors.initials: AK
authors.lastname: Lam
mesh_terms: D002461:Cell Line, Transformed; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D009061:Mouth Mucosa / Q000166:cytology; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D013234:Stem Cells / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D034741:RNA, Small Interfering; D014746:Vimentin; D063150:Polycomb Repressive Complex 1; C509186:TERT protein, human; D019098:Telomerase
keywords: BMI-1; EMT; Immortalisation; hTERT