Exosomal lncRNA USP30-AS1 activates the Wnt/β-catenin signaling pathway to promote cervical cancer progression via stabilization of β-catenin by USP30

IF 3.2 3区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Biotechnology Journal Pub Date : 2024-07-16 DOI:10.1002/biot.202300653

Chi Chi, Xiuwu Tang, Wei Liu, Ying Zhou, Rong Jiang, Youguo Chen, Min Li

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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.

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外泌体 lncRNA USP30-AS1 通过 USP30 稳定β-catenin，激活 Wnt/β-catenin 信号通路，促进宫颈癌的进展。

宫颈癌（CC）仍然是全球妇女癌症相关死亡的主要原因。长非编码 RNA（lncRNA）在包括宫颈癌在内的各种癌症中发挥着重要的调控作用。本研究调查了一种新型lncRNA--USP30反义RNA 1（USP30-AS1）在CC肿瘤发生中的功能。我们使用 RT-qPCR 分析了 USP30-AS1 的表达，并进行了体外功能缺失试验和体内试验，以评估 USP30-AS1 沉默对 CC 细胞生长和迁移的影响。我们还进行了其他机理实验，包括 RNA 拉取、RNA 免疫沉淀（RIP）和共免疫沉淀（Co-IP）实验，以阐明 USP30-AS1 的调控机制。我们发现 USP30-AS1 在 CC 组织和细胞中过表达。沉默 USP30-AS1 能显著减少细胞增殖、迁移、侵袭和肿瘤生长。此外，研究还发现USP30-AS1通过疏导microRNA-2467-3p（miR-2467-3p）和招募FUS RNA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-catenin并激活Wnt/β-catenin信号通路。这些发现表明，USP30-AS1通过miR-2467-3p/FUS/USP30轴增强了CC细胞的生长和迁移，突显了其作为CC生物标记物的潜力。

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来源期刊

Biotechnology Journal Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

8.90

自引率

2.10%

发文量

123

审稿时长

1.5 months

期刊介绍： Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances. In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office. BTJ promotes a special emphasis on: Systems Biotechnology Synthetic Biology and Metabolic Engineering Nanobiotechnology and Biomaterials Tissue engineering, Regenerative Medicine and Stem cells Gene Editing, Gene therapy and Immunotherapy Omics technologies Industrial Biotechnology, Biopharmaceuticals and Biocatalysis Bioprocess engineering and Downstream processing Plant Biotechnology Biosafety, Biotech Ethics, Science Communication Methods and Advances.