Nuclear-enriched RNA-binding proteins (RBPs) are mainly involved in transcriptional regulation, which is a critical checkpoint to tune gene diversity and expression levels. We analyzed nuclear RBPs in human HCC tissues and matched normal control tissues. Based on the gene expression levels, PTBP3 was identified as top-ranked in the nuclei of HCC cells. HCC cell lines then were transfected with siRNAs or lentiviral vectors. PTBP3 promoted HCC cell proliferation and metastasis both in vitro and in vivo. RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and qRT-PCR assays verified that PTBP3 protein recruited abundant lnc-NEAT1 splicing variants (NEAT1_1 and NEAT1_2) and pre-miR-612 (precursor of miR-612) in the nucleus. NEAT1_1, NEAT1_2 and miR-612 expression levels were determined by PTBP3. Correlational analyses revealed that PTBP3 was positively correlated with NEAT1, but it was inversely correlated with miR-612 in HCC. The P53/CCND1 and AKT2/EMT pathways were determined by NEAT1 and miR-612 respectively in HCC. The PTBP3^high and NEAT1^high/miR-612^low patients had a shorter overall survival. Therefore, nuclear-enriched RBP, PTBP3, promotes HCC cell malignant growth and metastasis by regulating the balance of splicing variants (NEAT1_1, NEAT1_2 and miR-612) in HCC.

中文翻译：

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PTBP3 剪接因子通过破坏 NEAT1 和 pre-miR-612 的剪接平衡促进肝细胞癌发生。

核富集的 RNA 结合蛋白 (RBP) 主要参与转录调控，这是调节基因多样性和表达水平的关键检查点。我们分析了人类 HCC 组织和匹配的正常对照组织中的核 RBP。基于基因表达水平，PTBP3 被鉴定为在 HCC 细胞的细胞核中排名靠前。然后用 siRNA 或慢病毒载体转染 HCC 细胞系。PTBP3 在体外和体内均促进 HCC 细胞增殖和转移。RNA 免疫沉淀 (RIP)、荧光原位杂交 (FISH) 和 qRT-PCR 分析证实 PTBP3 蛋白在细胞核中募集了丰富的 lnc-NEAT1 剪接变体（NEAT1_1 和 NEAT1_2）和 pre-miR-612（miR-612 的前体） . NEAT1_1、NEAT1_2 和 miR-612 表达水平由 PTBP3 确定。相关分析显示，PTBP3 与 NEAT1 呈正相关，但与 HCC 中的 miR-612 呈负相关。P53/CCND1 和 AKT2/EMT 通路分别由 HCC 中的 NEAT1 和 miR-612 决定。PTBP3^高和 NEAT1^高/miR-612^低患者的总生存期较短。因此，核富集的 RBP PTBP3 通过调节 HCC 中剪接变异体（NEAT1_1、NEAT1_2 和 miR-612）的平衡来促进 HCC 细胞的恶性生长和转移。