STAU1-mediated CNBP mRNA degradation by LINC00665 alters stem cell characteristics in ovarian cancer.

IF 5.7 2区生物学 Q1 BIOLOGY

Biology Direct Pub Date : 2024-07-30 DOI:10.1186/s13062-024-00506-w

Xiaofang Liu, Yang Chen, Ying Li, Jinling Bai, Zhi Zeng, Min Wang, Yaodong Dong, Yingying Zhou

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引用次数: 0

Abstract

Background: To investigate the role of lncRNA LINC00665 in modulating ovarian cancer stemness and its influence on treatment resistance and cancer development.

Methods: We isolated ovarian cancer stem cells (OCSCs) from the COC1 cell line using a combination of chemotherapeutic agents and growth factors, and verified their stemness through western blotting and immunofluorescence for stem cell markers. Employing bioinformatics, we identified lncRNAs associated with ovarian cancer, with a focus on LINC00665 and its interaction with the CNBP mRNA. In situ hybridization, immunohistochemistry, and qPCR were utilized to examine their expression and localization, alongside functional assays to determine the effects of LINC00665 on CNBP.

Results: LINC00665 employs its Alu elements to interact with the 3'-UTR of CNBP mRNA, targeting it for degradation. This molecular crosstalk enhances stemness by promoting the STAU1-mediated decay of CNBP mRNA, thereby modulating the Wnt and Notch signaling cascades that are pivotal for maintaining CSC characteristics and driving tumor progression. These mechanistic insights were corroborated by a series of in vitro assays and validated in vivo using tumor xenograft models. Furthermore, we established a positive correlation between elevated CNBP levels and increased disease-free survival in patients with ovarian cancer, underscoring the prognostic value of CNBP in this context.

Conclusions: lncRNA LINC00665 enhances stemness in ovarian cancer by mediating the degradation of CNBP mRNA, thereby identifying LINC00665 as a potential therapeutic target to counteract drug resistance and tumor recurrence associated with CSCs.

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LINC00665 介导的 STAU1 CNBP mRNA 降解可改变卵巢癌干细胞的特征。

背景：研究lncRNA LINC00665在调节卵巢癌干性中的作用及其对治疗耐药性和癌症发展的影响：研究lncRNA LINC00665在调节卵巢癌干性中的作用及其对治疗耐药性和癌症发展的影响：我们使用化疗药物和生长因子从COC1细胞系中分离出卵巢癌干细胞（OCSCs），并通过Western印迹和免疫荧光检测干细胞标记物验证其干性。利用生物信息学，我们确定了与卵巢癌相关的lncRNA，重点是LINC00665及其与CNBP mRNA的相互作用。我们利用原位杂交、免疫组化和 qPCR 检查了它们的表达和定位，并通过功能测试确定了 LINC00665 对 CNBP 的影响：结果：LINC00665利用其Alu元件与CNBP mRNA的3'-UTR相互作用，使其降解。这种分子串扰通过促进STAU1介导的CNBP mRNA衰变来增强干性，从而调节Wnt和Notch信号级联，而Wnt和Notch信号级联是维持CSC特征和推动肿瘤进展的关键。这些机理观点得到了一系列体外实验的证实，并通过肿瘤异种移植模型在体内得到了验证。结论：lncRNA LINC00665通过介导CNBP mRNA的降解增强卵巢癌的干性，从而将LINC00665确定为潜在的治疗靶点，以对抗与CSCs相关的耐药性和肿瘤复发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology Direct 生物-生物学

CiteScore

6.40

自引率

10.90%

发文量

审稿时长

7 months

期刊介绍： Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.