Xiamen Humanity Hospital Fujian Medical University, Xiamen City, Fujian Province, 361000, P.R. China.
Meng Chao Hepatobiliary Hospital of Fujian Medical University, Fuzhou City, Fujian Province, 350025, P.R. China.
Crit Rev Eukaryot Gene Expr. 2022;32(1):1-9. doi: 10.1615/CritRevEukaryotGeneExpr.2021039224.
TPT1 Antisense RNA 1 (TPT1-AS1) is a recently identified tumor oncogenic long non-coding RNA (lncRNA) in ovarian cancer and cervical cancer. This study was carried out to study the role of lncRNA TPT1-AS1 in hepatocellular carcinoma (HCC). Samples of HCC and non-tumor tissues derived from 62 HCC patients were subjected to RNA isolation and reverse transcription quantitative polymerase chain reaction to detect the differential expression of TPT1-AS1 and cyclin dependent kinase 2 (CDK2) in HCC. Correlations between the expression of TPT1-AS1 and CDK2 were analyzed by linear regression. TPT1-AS1 and CDK2 were overexpressed in SNU-398 and SU.86.86 cells to explore their relationship. The role of TPT1-AS1 and CDK2 in regulating the cell cycle progression and proliferation of SNU-398 and SU.86.86 cells was explored by cell cycle assay and cell proliferation assay, respectively. In addition, xenograft tumor formation was also carried out to further verify the TPT1-AS1 role in HCC in vivo. It was found that TPT1-AS1 was downregulated in HCC and inversely correlated with CDK2. The expression of TPT1-AS1 in HCC tissues was not affected by age, sex, AFP, HBV, HCV, and cirrhosis infection but was downregulated by clinical stages. In HCC cells, overexpression of TPT1-AS1 mediated the downregulation of CDK2, while silencing of TPT1-AS1 mediated the upregulation of CDK2. In cell proliferation assay, overexpression of TPT1-AS1 mediated the decreased proliferation rates, while silencing of TPT1-AS1 mediated the increased proliferation rates of HCC cells, while overexpression of CDK2 played an opposite role. In addition, overexpression of TPT1-AS1 reduced tumor growth in vivo. Therefore, overexpression of TPT1-AS1 may suppress HCC cell proliferation by downregulating CDK2.
TPT1 反义 RNA1（TPT1-AS1）是一种最近在卵巢癌和宫颈癌中发现的肿瘤致癌长非编码 RNA（lncRNA）。本研究旨在研究 lncRNA TPT1-AS1 在肝细胞癌（HCC）中的作用。对 62 例 HCC 患者的 HCC 组织和非肿瘤组织样本进行 RNA 分离和逆转录定量聚合酶链反应，以检测 HCC 中 TPT1-AS1 和细胞周期蛋白依赖性激酶 2（CDK2）的差异表达。通过线性回归分析 TPT1-AS1 和 CDK2 表达之间的相关性。在 SNU-398 和 SU.86.86 细胞中过表达 TPT1-AS1 和 CDK2 以探讨它们之间的关系。通过细胞周期分析和细胞增殖分析分别探讨 TPT1-AS1 和 CDK2 调节 SNU-398 和 SU.86.86 细胞周期进程和增殖的作用。此外，还进行了异种移植肿瘤形成实验，以进一步验证 TPT1-AS1 在 HCC 体内的作用。结果发现，TPT1-AS1 在 HCC 中下调，与 CDK2 呈负相关。TPT1-AS1 在 HCC 组织中的表达不受年龄、性别、AFP、HBV、HCV 和肝硬化感染的影响，但受临床分期的下调。在 HCC 细胞中，过表达 TPT1-AS1 介导 CDK2 的下调，而 TPT1-AS1 沉默则介导 CDK2 的上调。在细胞增殖实验中，过表达 TPT1-AS1 介导 HCC 细胞增殖率降低，而 TPT1-AS1 沉默则介导 HCC 细胞增殖率升高，而过表达 CDK2 则起到相反的作用。此外，过表达 TPT1-AS1 可减少体内肿瘤生长。因此，过表达 TPT1-AS1 可能通过下调 CDK2 抑制 HCC 细胞增殖。
