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circMRPL35 promotes gastric cancer progression through the miR-6809-3p/ZNF90 axis and affects the EMT process and

Xiuping Wang1,2, Zhendong Yao3, Yu Liu4

  • 1Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Jiangsu, 215300, China.

Non-Coding RNA Research
|November 13, 2025
PubMed
Abstract

Insights

Circular RNA circMRPL35 promotes gastric cancer (GC) by sponging miR-6809-3p to upregulate ZNF90. This axis influences epithelial-mesenchymal transition and the TGF-β1/SMAD pathway, driving GC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
  • The specific function of circMRPL35 in gastric cancer (GC) pathogenesis was previously undefined.

Purpose of the Study:

  • To investigate the role and mechanism of circMRPL35 in gastric cancer.
  • To elucidate the relationship between circMRPL35, miR-6809-3p, and ZNF90 in GC progression.

Main Methods:

  • Differential expression analysis of circMRPL35 using public gene expression datasets (GSE78092, GSE131414, GSE100170).
  • Experimental validation of circMRPL35 origin, localization, and function in GC cells (RNA assays, loss/gain-of-function).
  • Analysis of epithelial-mesenchymal transition (EMT) and TGF-β1/SMAD signaling pathway modulation (Western blot, immunofluorescence).
  • In vivo assessment using subcutaneous tumor models in nude mice.
  • Confirmation of molecular interactions using luciferase reporter and rescue assays.

Main Results:

  • circMRPL35 was identified as upregulated in GC tissues and cells, originating from the cyclization of exons 4 and 5.
  • circMRPL35 and ZNF90 were upregulated, while miR-6809-3p was downregulated in GC.
  • circMRPL35 and ZNF90 promoted GC cell migration, invasion, and suppressed apoptosis by modulating EMT and the TGF-β1/SMAD2/3 pathway.
  • circMRPL35 acts as a molecular sponge for miR-6809-3p, thereby regulating ZNF90 expression and enhancing GC cell phenotypes.

Conclusions:

  • circMRPL35 functions as an oncogenic driver in gastric cancer.
  • The circMRPL35/miR-6809-3p/ZNF90 axis is a key regulator of EMT and TGF-β1/SMAD signaling in GC.
  • circMRPL35 promotes GC progression through the identified molecular axis.
Keywords:
Gastric cancerTGF-β1/SMAD2/3ZNF90circMRPL35miR-6809-3p

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