Polypyrimidine tract-binding protein 1 (PTBP1) is one of the most investigated multifunctional RNA-binding proteins (RBP), controlling almost all steps of mRNA metabolism and processing. It has been reported that PTBP1 is overexpressed in many different types of cancer and this high expression is associated with increased proliferation and poor prognoses. However, there are no reports on a putative role for PTBP1 in the molecular abnormalities and pathogenesis of hepatocellular carcinoma (HCC). Here, we identified PTBP1 as a positive regulator of human HCC growth. The expression of PTBP1 was increased in human HCC cells and tissues compared to the corresponding controls, and this high expression was positively correlated with increased tumor size and a reduced survival rate. Mechanistically, PTBP1 enhanced cyclin D3 (CCND3) translation by interacting with the 5'-untranslated region (5'-UTR) of CCND3 mRNA, consequently facilitating cell cycle progression and tumor growth. Furthermore, we found that miR-194 inhibits PTBP1 expression by binding to the 3'-UTR of PTBP1 mRNA, resulting in reduced CCND3 levels and HCC cell growth; moreover, the levels of PTBP1 were negatively correlated with miR-194 levels in HCC. Taken together, these findings identify PTBP1 as a pivotal enhancer of HCC growth; the miR-194/PTBP1/CCND3 axis seemingly has a crucial role in the development and progression of HCC and targeting the axis could be a novel therapeutic strategy against human HCC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

中文翻译：

---

miR-194 / PTBP1 / CCND3轴可调节人肝细胞癌中的肿瘤生长。

聚嘧啶束结合蛋白1（PTBP1）是研究最多的多功能RNA结合蛋白（RBP）之一，它控制着mRNA代谢和加工的几乎所有步骤。据报道，PTBP1在许多不同类型的癌症中过表达，这种高表达与增殖增加和不良预后有关。但是，尚无关于PTBP1在肝细胞癌（HCC）分子异常和发病机制中的假定作用的报道。在这里，我们确定PTBP1为人类HCC生长的正调节剂。与相应的对照相比，PTBP1在人HCC细胞和组织中的表达增加，而这种高表达与肿瘤大小的增加和存活率的降低呈正相关。机械上，PTBP1通过与CCND3 mRNA的5'-非翻译区（5'-UTR）相互作用来增强细胞周期蛋白D3（CCND3）的翻译，从而促进细胞周期进程和肿瘤生长。此外，我们发现miR-194通过与PTBP1 mRNA的3'-UTR结合来抑制PTBP1的表达，导致CCND3水平降低和HCC细胞生长。此外，肝癌中PTBP1的水平与miR-194水平呈负相关。综上所述，这些发现确定PTBP1是肝癌生长的关键促进剂。miR-194 / PTBP1 / CCND3轴似乎在HCC的发生和发展中起着至关重要的作用，靶向该轴可能是针对人类HCC的一种新型治疗策略。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 -UTR），从而促进细胞周期进程和肿瘤生长。此外，我们发现miR-194通过与PTBP1 mRNA的3'-UTR结合来抑制PTBP1的表达，导致CCND3水平降低和HCC细胞生长。此外，肝癌中PTBP1的水平与miR-194水平呈负相关。综上所述，这些发现确定PTBP1是肝癌生长的关键促进剂。miR-194 / PTBP1 / CCND3轴似乎在HCC的发生和发展中起着至关重要的作用，靶向该轴可能是针对人类HCC的一种新型治疗策略。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 -UTR），从而促进细胞周期进程和肿瘤生长。此外，我们发现miR-194通过与PTBP1 mRNA的3'-UTR结合来抑制PTBP1的表达，导致CCND3水平降低和HCC细胞生长。此外，肝癌中PTBP1的水平与miR-194水平呈负相关。综上所述，这些发现确定PTBP1是肝癌生长的关键促进剂。miR-194 / PTBP1 / CCND3轴似乎在HCC的发生和发展中起着至关重要的作用，靶向该轴可能是针对人类HCC的一种新型治疗策略。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 PTBP1 mRNA的-UTR，导致CCND3水平降低和HCC细胞生长；此外，肝癌中PTBP1的水平与miR-194水平呈负相关。综上所述，这些发现确定PTBP1是肝癌生长的关键促进剂。miR-194 / PTBP1 / CCND3轴似乎在HCC的发生和发展中起着至关重要的作用，靶向该轴可能是针对人类HCC的一种新型治疗策略。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 PTBP1 mRNA的-UTR，导致CCND3水平降低和HCC细胞生长；此外，肝癌中PTBP1的水平与miR-194水平呈负相关。综上所述，这些发现确定PTBP1是肝癌生长的关键促进剂。miR-194 / PTBP1 / CCND3轴似乎在HCC的发生和发展中起着至关重要的作用，靶向该轴可能是针对人类HCC的一种新型治疗策略。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 miR-194 / PTBP1 / CCND3轴似乎在HCC的发生和发展中起着至关重要的作用，靶向该轴可能是针对人类HCC的一种新型治疗策略。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 miR-194 / PTBP1 / CCND3轴似乎在HCC的发生和发展中起着至关重要的作用，靶向该轴可能是针对人类HCC的一种新型治疗策略。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版