Circular RNA Hsa_circ_0007376 Promotes Malignancy of Gastric Cancer Cells by Regulating MiR-556-5p/CREB5 Axis

Circular RNA Hsa_circ_0007376 Promotes Malignancy of Gastric Cancer Cells by Regulating MiR-556-5p/CREB5 Axis

Chao Liu,¹ Xin Zhou,¹ Guangsheng Wang,¹ Chenyu Zhu¹ and Rui Xu¹

¹Department of Gastrointestinal Surgery, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China

Gastric cancer (GC) is one deadly malignancy globally. The potential clinical values of circular RNAs (circRNAs) in cancer diagnosis, prognosis, and treatment have been demonstrated in increasing studies. This research aimed at delving into the specific role of circRNA hsa_circ_0007376 (circMAP2K2) in GC development. CircMAP2K2, miR-556-5p, and CREB5 levels in GC cells and tissues were tested by RT-qPCR. Subcellular fractionation assay was employed for determining the distribution of circMAP2K2 in GC cell cytoplasm and nucleus. The binding potentials between circMAP2K2 (or CREB5) and miR-556-5p were confirmed through luciferase reporter assay. GC cell viability, growth, and metastasis were examined via CCK-8, colony formation, and Transwell assays. CREB5 protein level was assessed via western blot analysis. CircMAP2K2 was upregulated in GC cells and tissues vs. normal controls. CircMAP2K2 depletion hindered GC cell growth, migration, and invasion. Mechanically, circMAP2K2 elevated CREB5 level by completely binding with miR-556-5p. Overexpressing CREB5 abrogated the suppression of circMAP2K2 silencing on GC cell malignant behaviors. CircMAP2K2/miR-556-5p/CREB5 axis plays an oncogenic role in GC tumorigenesis.

Key words —— CREB5; gastric cancer; hsa_circ_0007376; metastasis; miR-556-5p; proliferation

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Tohoku J. Exp. Med., 2025 May, 266(2), 173-184.

Correspondence: Rui Xu, Department of Gastrointestinal Surgery, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, No.183, Yiling Road, Yichang, Hubei 443000, China.

e-mail: xruiu@hotmail.com