Abstract：
Long non-coding RNAs (lncRNAs) are key modulators during cancer progression. Application of using lncRNA expression to evaluate patient prognosis and sensitivity to treatment is highly anticipated, yet the expression and mechanism of many lncRNAs remain unknown. Herein, we projected for the investigation of TPT1-AS1 function in breast cancer. TPT1-AS1 was assessed by bioinformatic analysis of publicly available datasets and quantitative real-time PCR (qRT-PCR). Cell sensitivity to paclitaxel and cell proliferation was measured by flow cytometry and CCK-8. Interaction among TPT1-AS1, microRNA (miRNA, miR)-3156-5p and Caspase 2 (CASP2) was studied by bioinformatic analysis, qRT-PCR, western blot as well as dual luciferase reporter assay. Herein, TPT1-AS1 was significantly diminished in breast cancer from publicly available datasets and our collected samples. In breast cancer cells, TPT1-AS1 overexpression repressed cell proliferation and sensitized breast cancer cells to paclitaxel. RegRNA 2.0 predicted a potential interaction between TPT1-AS1 and miR-3156-5p which was confirmed by qRT-PCR as well as dual luciferase reporter assay. CASP2, a proapoptotic gene, was corroborated to be targeted by miR-3156-5p. Meanwhile, TPT1-AS1 upregulated CASP2 in breast cancer cells, and its biological function was reversed by CASP2 knockdown. Collectively, TPT1-AS1 diminished cell proliferation and sensitized cells to chemotherapy by sponging miR-3156-5p and upregulating CASP2, acting as a biomarker for patients with breast cancer.
摘要：
长链非编码RNA(lncRNA)是癌症进展过程中的关键调节剂。使用lncRNA表达来评估患者的预后和对治疗的敏感性是非常值得期待的。然而，许多lncRNAs的表达和机制仍然未知。在这里，我们预计TPT1-AS1在乳腺癌中的功能研究。通过公开可用数据集的生物信息学分析和定量实时PCR(qRT-PCR)评估TPT1-AS1。通过流式细胞术和CCK-8测量对紫杉醇和细胞增殖的细胞敏感性。TPT1-AS1，microRNA（miRNA，通过生物信息学分析研究了miR）-3156-5p和Caspase2（CASP2），qRT-PCR,蛋白质印迹以及双荧光素酶报告分析。在这里，从公开可用的数据集和我们收集的样本来看，TPT1-AS1在乳腺癌中显著减少。在乳腺癌细胞中，TPT1-AS1过表达抑制细胞增殖并使乳腺癌细胞对紫杉醇敏感。RegRNA2.0预测了TPT1-AS1和miR-3156-5p之间的潜在相互作用，这通过qRT-PCR以及双荧光素酶报告测定得到证实。CASP2，一个促凋亡基因，被证实是miR-3156-5p靶向的。同时,TPT1-AS1上调乳腺癌细胞中的CASP2，其生物学功能被CASP2敲除逆转。总的来说，TPT1-AS1通过生成miR-3156-5p和上调CASP2来减少细胞增殖并使细胞对化疗敏感，作为乳腺癌患者的生物标志物。
