Abstract：
Prostate cancer (PCa) is a common cancer and the leading cause of cancer-related death in men. To investigate the role of pre-mRNA processing factor 19 (PRPF19) in proliferation, migration of PCa, and evaluate the potential ability of PRPF19 as a therapeutic target. PRPF19 expression was analyzed from The Cancer Genome Atlas and GEPIA databank. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the transcription of PRPF9 and solute carrier family 40 member 1 (SLC40A1). Immunohistochemistry (IHC) was used to test PRPF9 expression in PCa tissues. The cell viability and 5-ethynyl-2\'-deoxyuridine incorporation analysis were performed to assess cell proliferation. Transwell assay was performed to investigate the migration and invasion of cancer cells. Western blot was used to measure the expression level of PRPF9, E-cadherin, Vimentin and α-smooth muscle actin (α-SMA), SLC40A1, LC3, Beclin-1 and ATG7. Immunofluorescence assay was performed to measure LC3 expression in PCa cells. The bioinformatic analysis revealed PRPF19 was highly expressed in PCa which was certified by qRT-PCR, western blot and IHC detection in PCa tissues. The proliferation of PCa cells could be promoted by PRPF19 overexpression and suppressed by PRPF19 knockdown. Moreover, the migration and invasion of PCa cells could be positively regulated by PRPF19 which promoted the expression of E-cadherin, Vimentin, and α-SMA. Furthermore, the expression of LC3, Beclin-1, and ATG7 was negatively regulated by PRPF19, indicating that PRPF19 inhibited autophagy in PCa cells. In the double knockdown of PRPF19 and SLC40A1, PRPF19 repressed the mRNA and reduced protein level of SLC40A1, and SLC40A1 antagonized effects of PRPF19 on proliferation, migration and autophagy of PCa cells. PRPF19 promoted proliferation and migration, and inhibited autophagy in PCa by attenuating SLC40A1 expression, indicating PRPF19 was a potential therapeutic target for PCa treatment.
摘要：
前列腺癌（PCa）是一种常见的癌症，也是男性癌症相关死亡的主要原因。探讨前mRNA加工因子19(PRPF19)在细胞增殖中的作用,PCa的迁移，并评估PRPF19作为治疗靶点的潜在能力。从癌症基因组图谱和GEPIA数据库分析PRF19表达。进行定量实时聚合酶链反应（qRT-PCR）以评估PRPF9和溶质载体家族40成员1（SLC40A1）的转录。免疫组织化学(IHC)用于检测PCa组织中的PRPF9表达。进行细胞活力和5-乙炔基-2'-脱氧尿苷掺入分析以评估细胞增殖。进行Transwell分析以研究癌细胞的迁移和侵袭。Westernblot检测PRPF9、E-cadherin、波形蛋白和α-平滑肌肌动蛋白（α-SMA），SLC40A1、LC3、Beclin-1和ATG7。进行免疫荧光测定以测量PCa细胞中的LC3表达。生物信息学分析显示，PRFP19在PCa中高表达，qRT-PCR证明，PCa组织中的westernblot和IHC检测。PRF19过表达可以促进PCa细胞的增殖，而PRF19敲低可以抑制PCa细胞的增殖。此外，PRF19可促进E-cadherin的表达,从而促进PCa细胞的迁移和侵袭,Vimentin,和α-SMA。此外，PRF19负调控LC3、Beclin-1和ATG7的表达,表明PRFP19抑制PCa细胞的自噬。在PRPF19和SLC40A1的双重敲除中，PRPF19抑制了SLC40A1的mRNA并降低了蛋白水平，SLC40A1拮抗了PRPF19的增殖作用，PCa细胞的迁移和自噬。PRPF19促进了扩散和迁移，并通过减弱SLC40A1表达来抑制PCa的自噬，提示PRF19是PCa治疗的潜在治疗靶点.
