端粒是位於染色體末端的一段DNA重複序列，用於保持染色體的完整性和控制細胞分裂周期。每當細胞進行分裂，端粒的長度就縮短一些，一旦端粒長度短到一定程度，細胞則會停止生長甚至進入細胞凋亡，這稱為複製老化。然而，大多數癌細胞能無限制地複製是因為端粒酶(telomerase)的活性被激活，根據研究指出，端粒酶在幹細胞以及癌細胞中的活性較高，而在體細胞幾乎不表現，因此對於癌症治療端粒酶能做為良好的標靶。端粒酶是由RNA (端粒酶RNA，TERC)以及蛋白質(端粒酶活性催化部位，TERT)所組成的複合體，因此選擇端粒酶RNA的部分以及端粒酶活性催化部位進行標的。本研究藉由RNA干擾(RNA interference, RNAi)在多種癌細胞中(HeLa、MDA-MB-231、PC3)穩定抑制端粒酶RNA分子的表現。首先，觀察穩定抑制端粒酶RNA表現的細胞株型態，顯示與對照組細胞形態上有明顯差異，此細胞形態較類似間質型細胞。接著，分析該細胞株生長以及爬行情況，實驗結果顯示，在第一代的靜默株中其生長速度與爬行能力與對照組之間並無差異，但從第五代之後，細胞生長速度較為緩慢、細胞週期分佈改變及細胞爬行能力明顯增加。有趣的是，利用西方墨點法(Western blot)分析一些蛋白質的表現情形，結果顯示，參與p53 路徑(hdm2、p53、p21)的蛋白質表現皆為下調，而在EMT相關標誌E-cadherin、-catenin等蛋白質表現皆明顯下降，指出TERC缺失會使細胞有EMT現象。綜合以上研究結果，TERC靜默株隨著代數增加，細胞生長受到影響且細胞爬行能力增加，因此將TERC作為癌症標的需注意是否會有EMT現象發生，而使癌細胞更惡化。

Telomeres at the ends of linear chromosomes protect chromosomes from degradation and repair activities which is essential for ensuring chromosome stability. When cells divide once, telomeres progressively become shorten until a few short telomeres become uncapped and end up leading to a growth arrest known as replicative aging. However, a classic cancer hallmark is the ability of malignant cells to proliferate unlimitedly that almost correlates with the telomerase activity. Cancer cells have the telomerase complex including a telomerase RNA component (TERC) and the reverse transcriptase catalytic subunit (TERT) that enable to overcome senescence by maintaining telomere lengths. Thus, TERC and TERT are the best targets for the development of mechanism-based cancer therapy. We established some stable TERC- knockdown cancer cell lines by RNAi (RNA interference), including HeLa (Cervical cancer), MDA-MB-231 (Breast cancer), and PC3 (Prostate cancer). The results show that loss of TERC expression would change the cell morphology, but cell proliferation rate and cell migration ability in the first and fifth passages are without significant differences. Interestingly, the cell proliferation rate decreases, but cell migration ability increases in tenth and twentieth passages. Western blot analysis indicates that p53 pathway (HDM2, p53, p21) and many types of cyclins are downregulated. The EMT marker like E-cadherin is also downregulated in TERC knockdown cells. We found that the level of senescence marker in twentieth passage TERC knockdown cells is higher than mock cancer cells by x-gal staining. In conclusion, loss of TERC increases cell migration ability, so we should take more considerations in cancer therapy when using TERC as a target.

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