細胞的品質監控系統包含DNA修復系統、監控RNA與維持蛋白質的恆定。先前的研究發現DNA修復系統及蛋白質的恆定在癌症中都有失調的情形，但RNA監控系統在癌症中所扮演的角色所知甚少。RNA exosome為RNA的品質管理系統，由核心次單元與酵素次單元組成，酵素次單元提供的核糖核酸酶的活性，可以將RNA降解或幫助形成成熟的RNA，其中表現最多的酵素次單元是RRP6，因此我們探討RRP6在乳癌中所扮演的角色。從Kaplan-Meier plotter 的分析中顯示EXO10RRP6表現越高對乳癌患者的預後較差，推測帶有RRP6的exosome complex可能在乳癌中帶來致癌的影響，為了了解RRP6可能調控哪些基因而造成細胞癌化，使用了Search-Based Exploration of Expression Compendium (SEEK)找出與RRP6在乳癌中共同表現的基因，發現mTOR與RRP6有最強的正相關， mTOR主要控制蛋白質的轉譯，由於mTOR使致癌基因高度表現，目前被視為乳癌中抗癌藥物重要標的。我們的結果顯示抑制RRP6表現降低mTOR的蛋白質，另外抑制了RNA exosome的核心次單元RRP4、RRP43、Csl4 和 EXOSC3也發現了mTOR蛋白質表現降低， 推測核心次單元可能參與RRP6調控mTOR的機制中。此外在抑制RRP6下，發現mTOR下游cyclin D1這個細胞生長指標下降，同時細胞的生長能力也減弱，當恢復mTOR表現，細胞的生長也回升。本研究顯示RRP6透過mTOR促進乳癌細胞生長並且提供了RNA監控系統與蛋白質轉譯間可能的交互作用。

Cellular strategies of quality control include DNA repair system, RNA surveillance machinery, and protein homeostasis. Previous studies have shown that DNA repair system and protein homeostasis are dysregulated in cancer, but the role of RNA surveillance system remains unclear. RNA exosome served as RNA quality control system consists of core subunits and enzymatic subunits. The enzymatic subunits execute the main function of RNA exosome in RNA degradation and maturation. Due to the predominance of RRP6 among three catalytic subunits in cell, we investigated the role of RRP6 in breast cancer. Analyzing by Kaplan-Meier plotter, patients with higher expression of EXO10RRP6 had poor prognosis, suggesting that RRP6-contained exosome complex mediates oncogenic effects in breast cancer. To identify RRP6-regulated genes, gene co-expression analysis was performed. In 5209 datasets, mechanistic target of rapamycin (mTOR) possesses the strongest correlation with RRP6 expression. mTOR, as a master translational control, is a drug target for breast cancer treatment. Our results indicated that knockdown of RRP6 decreases mTOR protein level. This effect was also observed upon knockdown of other core complex subunits such as RRP4, RRP43, Csl4 and EXOSC3, suggesting an exosome-dependent pathway is essential for mTOR regulation. Decreasing of mTOR downstream target, cyclin D1 and cell proliferation are through silencing of RRP6-mediated mTOR pathway. Taken together, our findings reveal the RRP6-mTOR axis in breast cancer cell proliferation and provide a possible crosstalk between RNA surveillance system and protein translation.

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