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STAU1-mediated CNBP mRNA degradation by LINC00665 alters stem cell characteristics in ovarian cancer.
Liu, Xiaofang; Chen, Yang; Li, Ying; Bai, Jinling; Zeng, Zhi; Wang, Min; Dong, Yaodong; Zhou, Yingying.
Afiliación
  • Liu X; Department of Anus and Intestine Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
  • Chen Y; Department of General Surgery, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, People's Republic of China.
  • Li Y; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
  • Bai J; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
  • Zeng Z; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
  • Wang M; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
  • Dong Y; Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China. dydlxf_1218@163.com.
  • Zhou Y; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China. zyy03300821@163.com.
Biol Direct ; 19(1): 59, 2024 Jul 30.
Article en En | MEDLINE | ID: mdl-39080743
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Células Madre Neoplásicas / Proteínas de Unión al ARN / Proteínas del Citoesqueleto / ARN Largo no Codificante Límite: Animals / Female / Humans Idioma: En Revista: Biol Direct Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Células Madre Neoplásicas / Proteínas de Unión al ARN / Proteínas del Citoesqueleto / ARN Largo no Codificante Límite: Animals / Female / Humans Idioma: En Revista: Biol Direct Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido