Open Access

ARTICLE

The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells

XUHUI ZHAO^1,2, XIAOMIN HUANG¹, CHUNYAN DANG², XIA WANG¹, YUJIAO QI³, HONGLING LI^2,*

1 The First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, China
2 Department of Oncology, Gansu People’s Hospital, Lanzhou, 730000, China
3 The Clinical Medical College, Ningxia Medical University, Ningxia, 750004, China

* Corresponding Author: HONGLING LI. Email:

(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research 2024, 32(5), 999-1009. https://doi.org/10.32604/or.2024.046679

Received 10 October 2023; Accepted 26 December 2023; Issue published 23 April 2024

Abstract

Background: EBV-miR-BARTs exhibit significant relevance in epithelial tumors, particularly in EBV-associated gastric and nasopharyngeal cancers. However, their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored. Material and Methods: Initially, EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines. Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45, and downregulation in EBV-positive cells (SUN-719). The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation, migration, and glycolytic processes, with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-β inhibitor. Results: EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells, while its target gene SMAD4 demonstrates downregulated expression. Upregulation of it can promote the proliferation and migration of gastric cancer cells. Additionally, We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells. Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells, concomitant with a diminished glycolytic capacity. Conclusion: In this study, we found that EBV-miRNA-BART6-5p can target SMAD4, effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway, thereby enhancing the proliferation and metastasis of gastric cancer cells. Our findings may offer new insights into the metabolic aspects of gastric cancer.

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