Abstract：
Cervical cancer (CC) remains a major cause of cancer-related mortality among women globally. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in various cancers, including CC. This study investigates the function of a novel lncRNA, USP30 antisense RNA 1 (USP30-AS1), in CC tumorigenesis. We analyzed USP30-AS1 expression using RT-qPCR and conducted in vitro loss-of-function assays, as well as in vivo assays, to evaluate the effects of USP30-AS1 silencing on CC cell growth and migration. Additional mechanistic experiments, including RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP) assays, were performed to elucidate the regulatory mechanisms influenced by USP30-AS1. We discovered that USP30-AS1 is overexpressed in CC tissues and cells. Silencing USP30-AS1 significantly reduced cell proliferation, migration, invasion, and tumor growth. Moreover, USP30-AS1 was found to modulate the expression of ubiquitin-specific peptidase 30 (USP30) by sponging microRNA-2467-3p (miR-2467-3p) and recruiting the FUS RNA binding protein (FUS), thereby stabilizing β-catenin and activating the Wnt/β-catenin signaling pathway. These findings suggest that USP30-AS1 enhances CC cell growth and migration through the miR-2467-3p/FUS/USP30 axis, highlighting its potential as a biomarker for CC.
摘要：
宫颈癌（CC）仍然是全球女性癌症相关死亡的主要原因。长链非编码RNA（lncRNAs）在各种癌症中起着至关重要的调节作用，包括CC。本研究调查了一种新型lncRNA的功能，USP30反义RNA1（USP30-AS1），在CC肿瘤发生中。我们使用RT-qPCR分析了USP30-AS1的表达，并进行了体外功能丧失测定，以及体内测定，评价USP30-AS1沉默对CC细胞生长和迁移的影响。额外的机械实验，包括RNA下拉法,RNA免疫沉淀(RIP),和免疫共沉淀（Co-IP）测定，进行以阐明受USP30-AS1影响的调节机制。我们发现USP30-AS1在CC组织和细胞中过表达。沉默USP30-AS1显著降低细胞增殖，迁移,入侵,和肿瘤生长。此外，发现USP30-AS1通过海绵化microRNA-2467-3p（miR-2467-3p）和募集FUSRNA结合蛋白（FUS）来调节泛素特异性肽酶30（USP30）的表达，从而稳定β-连环蛋白并激活Wnt/β-连环蛋白信号通路。这些结果表明，USP30-AS1通过miR-2467-3p/FUS/USP30轴增强CC细胞生长和迁移，强调其作为CC生物标志物的潜力。
