Cancer Institute, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China.
Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
J Exp Clin Cancer Res. 2019 Jul 10;38(1):301. doi: 10.1186/s13046-019-1312-y.
Colorectal cancer (CRC) remains the fourth most common cause of cancer-related mortality worldwide. We aimed to identify key molecules and signalling pathways mediating CRC growth and metastasis. Polypyrimidine tract-binding protein 3 (PTBP3) is a member of PTB family. A prooncogenic role for PTBP3 has also been discovered in several kinds of tumors. However, the expression and biological functions of the PTBP3 are still unknown in CRC.
We analysed the expression levels of PTBP3 using tissue microarray containing 568 CRC tissues and corresponding non-tumor adjacent tissues. The correlations between the PTBP3 expression level and clinicopathological features were evaluated using the chi-square test. The functional characterization for the role and molecular mechanism of PTBP3 in CRC was investigated through a series of in vitro and in vivo experiments.
We showed that PTBP3 expression was increased in human CRC, and high PTBP3 expression was correlated with poor five-year overall survival and disease-free survival. Moreover, PTBP3 promoted tumor cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. PTBP3 enhanced HIF-1α protein expression by directly binding to the 5'UTR HIF-1α mRNA and activated translation of HIF-1α. Furthermore, HIF-1α was responsible for PTBP3-induced cell migration and invasion.
PTBP3 appears to be a novel oncogene of CRC through binding to the IRES region of HIF-1α mRNA, which regulates HIF-1α translation. PTBP3 can serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC.
结直肠癌（CRC）仍然是全球第四种常见的癌症相关死亡原因。我们旨在确定介导 CRC 生长和转移的关键分子和信号通路。多嘧啶 tract 结合蛋白 3（PTBP3）是 PTB 家族的一员。PTBP3 在几种肿瘤中也被发现具有致癌作用。然而，CRC 中 PTBP3 的表达和生物学功能尚不清楚。
我们使用包含 568 例 CRC 组织和相应非肿瘤相邻组织的组织微阵列分析了 PTBP3 的表达水平。使用卡方检验评估 PTBP3 表达水平与临床病理特征之间的相关性。通过一系列体外和体内实验研究了 PTBP3 在 CRC 中的作用和分子机制的功能特征。
我们表明，PTBP3 在人 CRC 中表达增加，高 PTBP3 表达与五年总体生存率和无病生存率差相关。此外，PTBP3 在体外促进肿瘤细胞增殖、迁移和侵袭，在体内促进肿瘤生长和转移。PTBP3 通过直接结合 HIF-1α mRNA 的 5'UTR 增强 HIF-1α 蛋白表达，并激活 HIF-1α 的翻译。此外，HIF-1α 负责 PTBP3 诱导的细胞迁移和侵袭。
PTBP3 通过与 HIF-1α mRNA 的 IRES 区域结合，调节 HIF-1α 的翻译，似乎成为 CRC 的一种新型癌基因。PTBP3 可以作为 CRC 患者复发和预后的有前途的预测生物标志物。
