circGAPVD1 inhibits the progression of gastric cancer through miR-4424/STK4 axis and encoding GAPVD1-137aa protein

Linqi Zhu; Zhendong Yao; Yun Liu; Shihe Shao; Wei Zhou; Jiawei Ding; Boneng Mao; Chen Shao; Feilun Cui

doi:10.1016/j.ijbiomac.2025.145408

circGAPVD1 inhibits the progression of gastric cancer through miR-4424/STK4 axis and encoding GAPVD1-137aa protein

Int J Biol Macromol. 2025 Jun 20;319(Pt 3):145408. doi: 10.1016/j.ijbiomac.2025.145408. Online ahead of print.

Authors

Linqi Zhu¹, Zhendong Yao², Yun Liu³, Shihe Shao³, Wei Zhou⁴, Jiawei Ding⁵, Boneng Mao⁶, Chen Shao⁷, Feilun Cui⁸

Affiliations

¹ Department of Clinical Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China; The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China; The Affiliated Taizhou Second People's Hospital of Yangzhou University, Taizhou, Jiangsu, China.
² The Affiliated Yixing Hospital of Jiangsu University, Wuxi, Jiangsu, China.
³ The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
⁴ Department of Clinical Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
⁵ Department of Clinical Laboratory, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, China.
⁶ The Affiliated Yixing Hospital of Jiangsu University, Wuxi, Jiangsu, China. Electronic address: maoboneng@163.com.
⁷ The Affiliated Hospital of Jiangsu University, Zhenjiang, China. Electronic address: shaochen84@163.com.
⁸ The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China; The Affiliated Taizhou Second People's Hospital of Yangzhou University, Taizhou, Jiangsu, China. Electronic address: pdcuifeilun@163.com.

PMID: 40545108
DOI: 10.1016/j.ijbiomac.2025.145408

Abstract

Background: Gastric cancer (GC) is a malignant gastrointestinal tumor that originates from the epithelium of the gastric mucosa, and circular RNA (circRNA) plays an important role in its progression.

Methods: The localization of circGAPVD1 and miR-4424 was determined using cytoplasmic RNA isolation and fluorescence in situ hybridization (FISH) assay. The expression levels of circGAPVD1, miR-4424 and mRNA transcripts were determined by quantitative real-time polymerase chain reaction (qPCR). The biological functions of circGAPVD1, miR-4424, serine/threonine kinase 4 (STK4) and GAPVD1-137aa in GC progression evaluated using Transwell, cell invasion, wound scratch assay, cell counting kit 8 (CCK-8), and flow cytometry assays. Protein expression levels were determined by Western blot analysis and immunofluorescence assay. The sponging interaction between circGAPVD1 and miR-4424 was validated using a dual-luciferase reporter assay. The effect of circGAPVD1 on tumor formation ability in vivo was evaluated in BALB/c nude mice with subcutaneous tumors, and the protein-coding potential was verified by induction and purification of proteins.

Results: circGAPVD1 and miR-4424 were localized in the nucleus and cytoplasm of GC cells. The expression level of circGAPVD1 in GC tissues was lower than that in paracancerous tissues, and was found to be associated with tumor tissue size and tumor node metastasis (TNM) stage. Survival curve analysis revealed that patients with high circGAPVD1 expression level had better prognosis. circGAPVD1 can adsorb miR-4424 through a sponging mechanism to regulate STK4 expression and suppressing GC cell progression. It was also determined that circGAPVD1 has the ability to encode amino acids and encodes the GAPVD1-137aa protein.

Conclusion: circGAPVD1 inhibits GC progression via the miR-4424/STK4 axis and encodes the GAPVD1-137aa protein, thereby inhibiting GC progression. This represents the comprehensive study linking circGAPVD1 to GC progression, patient survival outcomes, and therapeutic potential.

Keywords: Gastric cancer; STK4; circGAPVD1; miR-4424.