He Zhentao, Ni Qianhua, Li Xichun, Zhao Mingyu, Mo Qingguo, Duo Yongsheng
The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161099, China.
Heliyon. 2023 Jun 16;9(6):e17387. doi: 10.1016/j.heliyon.2023.e17387. eCollection 2023 Jun.
Aberrant alternative splicing is one of the important causes of cancer. Polypyrimidine tract binding protein 1 (PTBP1) has been found to be involved in splicing regulation in a variety of tumors. Here, we observed significant up-regulation of PTBP1 in primary hepatocellular carcinoma (HCC) tissues. High levels of PTBP1 expression were associated with poor prognosis and increased metastatic potential in HCC. studies demonstrated that elevated PTBP1 promoted both migration and invasion by HCC cells. In contrast, knockdown of PTBP1 significantly inhibited the migration and invasion of HCC cells . Further, up-regulation of PTBP1 markedly accumulated the expression of oncogenic isoform of NUMB, NUMB-PRR. We observed two isoforms of NUMB, NUMB-PRR and NUMB-PRR exhibit opposite function in HCC cells, which partially explain PTBP1 plays the tumor promoting roles in a NUMB splicing-dependent manner. In summary, our study indicates that PTBP1 may serve as an oncogene in HCC patients by regulating the alternative splicing of NUMB exon 9 and could potentially serve as a prognostic indicator.
异常可变剪接是癌症的重要病因之一。多嘧啶序列结合蛋白1（PTBP1）已被发现参与多种肿瘤的剪接调控。在此，我们观察到原发性肝细胞癌（HCC）组织中PTBP1显著上调。PTBP1的高表达水平与HCC的预后不良和转移潜能增加相关。研究表明，PTBP1升高促进了HCC细胞的迁移和侵袭。相反，敲低PTBP1显著抑制了HCC细胞的迁移和侵袭。此外，PTBP1的上调显著积累了致癌性NUMB异构体NUMB-PRR的表达。我们观察到NUMB的两种异构体NUMB-PRR和NUMB-PRR在HCC细胞中表现出相反的功能，这部分解释了PTBP1以NUMB剪接依赖的方式发挥促肿瘤作用。总之，我们的研究表明，PTBP1可能通过调节NUMB外显子9的可变剪接在HCC患者中作为癌基因起作用，并可能作为一种预后指标。
