Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Mol Cell Biochem. 2022 Oct;477(10):2451-2467. doi: 10.1007/s11010-022-04456-7. Epub 2022 May 18.
Alternative splicing is implicated in each of the hallmarks of cancer, and is mechanised by various splicing factors. Serine-Arginine Protein Kinase 1 (SRPK1) is an enzyme which moderates the activity of splicing factors rich in serine/arginine domains. Here we review SRPK1's relationship with various cancers by performing a systematic review of all relevant published data. Elevated SRPK1 expression correlates with advanced disease stage and poor survival in many epithelial derived cancers. Numerous pre-clinical studies investigating a host of different tumour types; have found increased SRPK1 expression to be associated with proliferation, invasion, migration and apoptosis in vitro as well as tumour growth, tumourigenicity and metastasis in vivo. Aberrant SRPK1 expression is implicated in various signalling pathways associated with oncogenesis, a number of which, such as the PI3K/AKT, NF-КB and TGF-Beta pathway, are implicated in multiple different cancers. SRPK1-targeting micro RNAs have been identified in a number of studies and shown to have an important role in regulating SRPK1 activity. SRPK1 expression is also closely related to the response of various tumours to platinum-based chemotherapeutic agents. Future clinical applications will likely focus on the role of SRPK1 as a biomarker of treatment resistance and the potential role of its inhibition.
选择性剪接与癌症的所有标志性特征都有关联,并且由各种剪接因子来实现。丝氨酸/精氨酸蛋白激酶 1(SRPK1)是一种调节富含丝氨酸/精氨酸结构域的剪接因子活性的酶。在这里,我们通过对所有相关已发表数据进行系统综述,回顾了 SRPK1 与各种癌症的关系。在许多上皮来源的癌症中,升高的 SRPK1 表达与晚期疾病阶段和不良预后相关。大量研究不同肿瘤类型的临床前研究发现,SRPK1 表达增加与体外增殖、侵袭、迁移和凋亡以及体内肿瘤生长、致瘤性和转移相关。异常的 SRPK1 表达与致癌相关的各种信号通路有关,其中一些信号通路,如 PI3K/AKT、NF-КB 和 TGF-β通路,与多种不同的癌症有关。在许多研究中已经鉴定出靶向 SRPK1 的 microRNAs,并显示它们在调节 SRPK1 活性方面具有重要作用。SRPK1 表达也与多种肿瘤对铂类化疗药物的反应密切相关。未来的临床应用可能将重点关注 SRPK1 作为治疗耐药性的生物标志物的作用及其抑制作用的潜在作用。