microRNA与肿瘤机制-培训课件.ppt

let-7f down-regulation The let-7 family of miRNA includes 14 isomers; each isomer is typically located on a different chromosome [8]. This study focused on let-7f, because it has been previously shown to inhibit proliferation of lung cancer cells [29]. We observed a reduced expression of let-7f mature miRNA in PCCL3 cells with activation of RET/ PTC3. This suggests that let-7f down-regulation is an important step in the biologic effects mediated by the RET/ PTC oncogene. reduce cell growth a previous study from patients with papillary carcinoma and normal thyroid tissues showed that let-7f is downregulated in this cancer [28]. To clarify the function of let-7f in the thyroid cancer, exogenous let-7f was overexpressed in TPC-1 papillary cancer cells that harbor the RET/PTC1 rearrangement. reduce cell growth Although transfection of let-7f in TPC-1 cells repressed ERK phosphorylation, significant modulation of K-RAS and H-RAS proteins was not observed after the induction of let-7f. Nevertheless, the modulation of genes related to cell cycle may explain, at least in part, the reduced cell growth of TPC-1 cells transfected with let-7f. enhance expression of differentiation markers During malignant progression, thyroid cancer cells undergo dedifferentiation, becoming more aggressive and refractory to treatment. We demonstrate that let-7f is able to enhance the expression of some of differentiation markers in TPC-1 cells, including TITF1.mice lacking this transcription factor are unable to develop a thyroid gland [33]. enhance expression of differentiation markers let-7 may also play an important role in thyroid development through the regulation of TITF1 expression. Therefore, it is evident that let-7f is critical for proper regulation of thyroid cell growth and differentiati