Department of General Surgery, The Center Hospital of Ezhou, Ezhou, China.
Department of Medical Laboratory, The Center Hospital of Ezhou, Ezhou, China.
Bosn J Basic Med Sci. 2021 Feb 1;21(1):39-46. doi: 10.17305/bjbms.2020.4470.
Long non-coding RNAs are considered to be critical regulators of tumor progression. Tumor protein translationally controlled 1 antisense RNA 1 (TPT1-AS1) was shown to have an oncogenic role in cervical and ovarian cancer. The clinical significance and biological function of TPT1-AS1 in gastric cancer (GC) are not clear. In this study, we analyzed the expression of TPT1-AS1 in GC tissues and cell lines and performed functional and mechanistic analysis of TPT1-AS1 effects on GC cell proliferation, migration, and invasion. TPT1-AS1 expression was determined in 76 pairs of GC tissues vs. matched adjacent normal tissues and in four GC cell lines (SGC-7901, AGS, BGC-823, and MGC-803) vs. GES-1 cell line by quantitative reverse transcription PCR. SGC-7901 and MGC-803 cells were transfected with small interfering RNA or scrambled negative control, and cell proliferation, colony formation, migration, invasion and cell cycle assays were performed. The expression of proteins involved in cell cycle progression and epithelial-mesenchymal transition was analyzed by Western blot. TPT1-AS1 expression was significantly higher in GC tissues and cell lines compared to controls. The overexpression of TPT1-AS1 was significantly correlated with TNM stage and lymph node metastasis, and it was associated with worse prognosis of GC patients according to the Kaplan-Meier survival analysis and Cox proportional hazard regression analysis. The knockdown of TPT1-AS1 significantly inhibited proliferation, cell cycle G1/S transition, migration, and invasion of SGC-7901 and MGC-803 cells. Moreover, TPT1-AS1 knockdown downregulated the expression of cyclin-dependent kinase (CDK) 4, cyclin D1, and vimentin and upregulated the expression of p21 and E-cadherin. Our findings suggest that TPT1-AS1 may be a promising therapeutic target in GC.
长链非编码 RNA 被认为是肿瘤进展的关键调节因子。肿瘤蛋白翻译控制 1 反义 RNA 1（TPT1-AS1）在宫颈癌和卵巢癌中表现出致癌作用。TPT1-AS1 在胃癌（GC）中的临床意义和生物学功能尚不清楚。在这项研究中，我们分析了 TPT1-AS1 在 GC 组织和细胞系中的表达，并对 TPT1-AS1 对 GC 细胞增殖、迁移和侵袭的影响进行了功能和机制分析。通过定量逆转录 PCR 检测 76 对 GC 组织与配对的相邻正常组织以及 4 种 GC 细胞系（SGC-7901、AGS、BGC-823 和 MGC-803）与 GES-1 细胞系中的 TPT1-AS1 表达。用小干扰 RNA 或阴性对照转染 SGC-7901 和 MGC-803 细胞，进行细胞增殖、集落形成、迁移、侵袭和细胞周期检测。通过 Western blot 分析参与细胞周期进程和上皮-间充质转化的蛋白质表达。与对照组相比，GC 组织和细胞系中的 TPT1-AS1 表达明显升高。TPT1-AS1 的过表达与 TNM 分期和淋巴结转移显著相关，根据 Kaplan-Meier 生存分析和 Cox 比例风险回归分析，与 GC 患者的预后不良相关。TPT1-AS1 敲低显著抑制 SGC-7901 和 MGC-803 细胞的增殖、细胞周期 G1/S 期转换、迁移和侵袭。此外，TPT1-AS1 敲低下调了细胞周期蛋白依赖性激酶（CDK）4、细胞周期蛋白 D1 和波形蛋白的表达，上调了 p21 和 E-钙粘蛋白的表达。我们的研究结果表明，TPT1-AS1 可能是 GC 的一个有前途的治疗靶点。
