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Liang YC has completed his PhD at the age of 32 years from National Taiwan University, Taiwan. He is the professor of Taipei Medical University, Taiwan. He has over 100 publications that have been cited over 5000 times, and his publication H-index is 37.
ZFP36 family members include ZFP36 (also named TTP and TIS11), ZFP36L1 (also called BRF1, ERF1, or TIS11B), and ZFP36L2 (also called BRF2, ERF2, and TIS11D), which belong to CCCH-type zinc finger proteins with two tandem zinc finger (TZF) regions. TTP was found to induce cell senescence by promoting p53 protein expression. However, it is unclear whether ZFP36L1 and ZFP36L2 have antiproliferative activities similar to that of TTP. In this study, a tetracycline-inducible (Tet-On) system was used to induce the expression of ZFP36L1 or ZFP36L2 in T-REx-293 cells by doxycycline (Dox) treatment. Three human colorectal cancer cell lines, HCT116 p53+/+, HCT116 p53-/-, and SW620 (mutated p53) cells, were used to overexpress the wild-type or TZF mutation of ZFP36L1 or ZFP36L2 gene as well as to knockdown the ZFP36L1 or ZFP36L2 gene by lentiviral vectors. When ZFP36L1 or ZFP36L2 was overexpressed, we found that cell proliferation was dramatically inhibited, but did not cause significant cell death. The induction of ZFP36L1 or ZFP36L2 resulted in cell cycle arrest at the G1 phase and an increase in p53 expression. In contrast, levels of cell cycle-related proteins including cyclin B, cyclin D, cyclin A, and p21 decreased in ZFP36L1- or ZFP36L2-overexpressing T-REx-293 cells. Forced expression of ZFP36L1 or ZFP36L2 also inhibited cell proliferation and cyclin D gene expression in these three kinds of cells; however, it increased p53 and p21 expressions only in HCT116 p53+/+ cells. On the other hand, knockdown of ZFP36L1 or ZFP36L2 increased cell proliferation and cyclin D expression, and mutation of the TZF of ZFP36L1 (C135/173R) or ZFP36L2 (C174/212R) caused them to lose their antiproliferative ability, such that they could not inhibit cyclin D expression in these three cell lines. The results suggest that ZFP36L1 and ZFP36L2 play a negative role in cell proliferation of human colorectal cancer cells, and the underlying mechanisms might be mediated through a cyclin D-dependent and p53-independent pathway