PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α
PTBP3 contributes to colorectal cancer growth and metastasis via translational activation of HIF-1α
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PTBP3 通过 HIF-1 α 的翻译激活促进结直肠癌的生长和转移
DOI：
10.1186/s13046-019-1312-y
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发表时间：
2019-07-10
影响因子：
11.3
通讯作者：
Bai, Jin
中科院分区：
文献类型：
--
作者：
Hou, Pingfu;Chen, Fang;Bai, Jin
背景：结直肠癌（CRC）仍然是全球癌症相关死亡的第四大常见原因。我们的目的是确定关键分子和信号通路介导CRC的生长和转移。多聚嘧啶片段结合蛋白3（PTBP 3）是PTB家族的一员。PTBP 3的促癌作用也已在几种肿瘤中发现。方法：采用组织芯片技术检测568例结直肠癌组织及相应癌旁组织中PTBP 3的表达水平。采用卡方检验评估PTBP 3表达水平与临床病理特征之间的相关性。通过一系列的体外和体内实验研究了PTBP 3在结直肠癌中的作用和分子机制的功能特征。结果：我们发现PTBP 3在人结直肠癌中表达增加，并且PTBP 3高表达与5年总生存率和无病生存率相关。此外，PTBP 3在体外促进肿瘤细胞的增殖、迁移和侵袭，在体内促进肿瘤的生长和转移。PTBP 3通过直接结合5 ' UTR HIF-1 α mRNA并激活HIF-1 α的翻译来增强HIF-1 α蛋白的表达。结论：PTBP 3可能是大肠癌的一个新的癌基因，它与HIF-1 α mRNA的IRES区域结合，调节HIF-1 α的翻译。PTBP 3可作为CRC患者复发和预后的有希望的预测生物标志物。
Background: 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.Methods: 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.Results: 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-1 alpha protein expression by directly binding to the 5 ' UTR HIF-1 alpha mRNA and activated translation of HIF-1 alpha. Furthermore, HIF-1 alpha was responsible for PTBP3-induced cell migration and invasion.Conclusions: PTBP3 appears to be a novel oncogene of CRC through binding to the IRES region of HIF-1 alpha mRNA, which regulates HIF-1 alpha translation. PTBP3 can serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC.