2. Academic Validation
  3. METTL3-mediated m6A modification of LINC00857 enhances stemness and metastasis of ovarian cancer cells by activating the YAP-TEAD pathway

METTL3-mediated m6A modification of LINC00857 enhances stemness and metastasis of ovarian cancer cells by activating the YAP-TEAD pathway

  • Sci Rep. 2025 Nov 20;15(1):41132. doi: 10.1038/s41598-025-24958-w.
Xueke Lin 1 2,  Yiting Hong 2,  Shengjun You 2,  Ping Li 2,  Yuchun Lv 2,  Jinyang Zheng 3,  Pengming Sun 4 5 6
Affiliations

Affiliations

  • 1 College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian, China.
  • 2 Department of Obstetrics and Gynecology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China.
  • 3 Department of Pathology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, Fujian, China.
  • 4 College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian, China. [email protected].
  • 5 Laboratory of Gynecologic Oncology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, 350001, Fujian, China. [email protected].
  • 6 Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, 350001, Fujian, China. [email protected].
PMID: 41266477 DOI: 10.1038/s41598-025-24958-w
Abstract

This study was designed to illustrate the mechanism underlying the up-regulation of LINC00857 expression and to identify novel molecular targets for the treatment of ovarian Cancer (OC). The LINC00857 and methyltransferase-like 3 (METTL3) expression levels were observed in clinical OC tissues and cells, and their correlation within tissues was analyzed. To further explore the relationship between LINC00857 and METTL3, a combined transfection of pcDNA3.1-LINC00857 and METTL3 siRNA was performed. Subsequently, cell invasion, viability, migration, and sphere-forming capabilities were assessed using Transwell, Cell Counting Kit-8, scratch and sphere-formation assays. Furthermore, western blot analysis was conducted to determine the expression of proteins related to Cancer cell stemness and the yes-associated protein (YAP) pathway. The relationship between LINC00857 and METTL3 was verified using the MeRIP-qPCR kit, RNA pull-down assay and RNA stability assay. Both LINC00857 and METTL3 demonstrated high expression levels in OC cells and tissues, with a positive correlation observed in clinical tissues. When knocking down the LINC00857 expression level, the invasion, migration, proliferation, and sphere-forming capabilities of cells were all notably reduced. Knocking down LINC00857 expression also markedly decreased the activity of the YAP pathway and the expression of proteins related to Cancer cell stemness. Overexpression of LINC00857 yielded opposite effects. When knocking down METTL3, the stability of LINC00857 and the modification level of N6-methyladenosine were remarkably decreased. Moreover, there was interaction between METTL3 and LINC00857. METTL3-mediated N6-methyladenosine modification of LINC00857 enhanced metastasis and stemness of OC cells via activating the YAP-TEA domain transcription factor pathway.

Keywords

Cancer stemness; LncRNA LINC00857; M6A modification; METTL3; Ovarian cancer; YAP-TEAD.

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