EBV-miR-BART14-3p Targets LACTB to Enhance Gastric Cancer Cell Proliferation and Migration

Overview

Journal Biochem Genet

Date 2025 Feb 4

PMID 39903432

Authors

Xiaomin Huang

Xuhui Zhao

Yujiao Qi

Tian Lan

Ruiling Wang

Shuang Liang

Yuxiu Ma

Cuixia Di

Hongling Li

Affiliations

Soon will be listed here.

Abstract

Epstein-Barr virus (EBV), the first human virus identified with oncogenic properties, encodes a class of microRNAs known as miR-BART (BamHI-A rightward transcript microRNAs). This study investigates the pivotal role of EBV-miR-BART14-3p in the progression of gastric cancer, particularly focusing on its effects on epithelial-mesenchymal transition (EMT), cell proliferation, and migration. EBV-associated gastric cancer (EBVaGC) is distinguished by unique genomic and epigenomic characteristics, with EBV miRNAs significantly influencing tumor biology by regulating gene expression. Our research demonstrates that EBV-miR-BART14-3p facilitates gastric cancer cell migration and invasion by targeting the tumor suppressor gene LACTB, which in turn activates the Phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, a critical driver of EMT. The suppression of LACTB in EBVaGC highlights its crucial role in inhibiting tumor progression. These findings position EBV-miR-BART14-3p as a key player in gastric cancer development and underscore its potential as both a prognostic biomarker and a therapeutic target for EBVaGC.

References

Abusalah M, Irekeola A, Shueb R, Jarrar M, Yean Yean C . Prognostic Epstein-Barr Virus (EBV) miRNA biomarkers for survival outcome in EBV-associated epithelial malignancies: Systematic review and meta-analysis. PLoS One. 2022; 17(4):e0266893. PMC: 9015129. DOI: 10.1371/journal.pone.0266893. View

Brabletz S, Schuhwerk H, Brabletz T, Stemmler M . Dynamic EMT: a multi-tool for tumor progression. EMBO J. 2021; 40(18):e108647. PMC: 8441439. DOI: 10.15252/embj.2021108647. View

Cai L, Ye Y, Jiang Q, Chen Y, Lyu X, Li J . Author Correction: Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma. Nat Commun. 2020; 11(1):3437. PMC: 7338543. DOI: 10.1038/s41467-020-17048-0. View

Chen Z, Yan S, Chen X, Zhang Q, Liu S, Liu Y . The genomic architecture of EBV and infected gastric tissue from precursor lesions to carcinoma. Genome Med. 2021; 13(1):146. PMC: 8422682. DOI: 10.1186/s13073-021-00963-2. View

Choy E, Siu K, Kok K, Lung R, Tsang C, To K . An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival. J Exp Med. 2008; 205(11):2551-60. PMC: 2571930. DOI: 10.1084/jem.20072581. View

Cucchi D, Mauro C . LACTB-mediated tumour suppression by increased mitochondrial lipid metabolism. Cell Death Differ. 2017; 24(7):1137-1139. PMC: 5520170. DOI: 10.1038/cdd.2017.60. View

Damania B, Kenney S, Raab-Traub N . Epstein-Barr virus: Biology and clinical disease. Cell. 2022; 185(20):3652-3670. PMC: 9529843. DOI: 10.1016/j.cell.2022.08.026. View

Diggins N, Hancock M . Viral miRNA regulation of host gene expression. Semin Cell Dev Biol. 2022; 146:2-19. PMC: 10101914. DOI: 10.1016/j.semcdb.2022.11.007. View

Dong M, Chen J, Huang J, Gong L, Shao C . The roles of EBV-encoded microRNAs in EBV-associated tumors. Crit Rev Oncol Hematol. 2019; 135:30-38. DOI: 10.1016/j.critrevonc.2019.01.014. View

10.

Dong M, Gong L, Chen J, Zhang X, Zhang Y, Hui D . EBV-miR-BART10-3p and EBV-miR-BART22 promote metastasis of EBV-associated gastric carcinoma by activating the canonical Wnt signaling pathway. Cell Oncol (Dordr). 2020; 43(5):901-913. DOI: 10.1007/s13402-020-00538-0. View

11.

Dongre A, Weinberg R . New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2018; 20(2):69-84. DOI: 10.1038/s41580-018-0080-4. View

12.

Epstein M, ACHONG B, BARR Y . VIRUS PARTICLES IN CULTURED LYMPHOBLASTS FROM BURKITT'S LYMPHOMA. Lancet. 1964; 1(7335):702-3. DOI: 10.1016/s0140-6736(64)91524-7. View

13.

Farrell P . Epstein-Barr Virus and Cancer. Annu Rev Pathol. 2018; 14:29-53. DOI: 10.1146/annurev-pathmechdis-012418-013023. View

14.

Fierti A, Bright Yakass M, Okertchiri E, Adadey S, Quaye O . The Role of Epstein-Barr Virus in Modulating Key Tumor Suppressor Genes in Associated Malignancies: Epigenetics, Transcriptional, and Post-Translational Modifications. Biomolecules. 2022; 12(1). PMC: 8773690. DOI: 10.3390/biom12010127. View

15.

Fukayama M, Abe H, Kunita A, Shinozaki-Ushiku A, Matsusaka K, Ushiku T . Thirty years of Epstein-Barr virus-associated gastric carcinoma. Virchows Arch. 2019; 476(3):353-365. DOI: 10.1007/s00428-019-02724-4. View

16.

Guo R, Gewurz B . Epigenetic control of the Epstein-Barr lifecycle. Curr Opin Virol. 2021; 52:78-88. PMC: 9112224. DOI: 10.1016/j.coviro.2021.11.013. View

17.

Hirabayashi M, Georges D, Clifford G, de Martel C . Estimating the Global Burden of Epstein-Barr Virus-Associated Gastric Cancer: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2022; 21(4):922-930.e21. DOI: 10.1016/j.cgh.2022.07.042. View

18.

Huang C, Liu H, Hu Y, Sun Y, Su X, Cao H . Laparoscopic vs Open Distal Gastrectomy for Locally Advanced Gastric Cancer: Five-Year Outcomes From the CLASS-01 Randomized Clinical Trial. JAMA Surg. 2021; 157(1):9-17. PMC: 8529527. DOI: 10.1001/jamasurg.2021.5104. View

19.

Joshi S, Badgwell B . Current treatment and recent progress in gastric cancer. CA Cancer J Clin. 2021; 71(3):264-279. PMC: 9927927. DOI: 10.3322/caac.21657. View

20.

Keckesova Z, Liu Donaher J, De Cock J, Freinkman E, Lingrell S, Bachovchin D . LACTB is a tumour suppressor that modulates lipid metabolism and cell state. Nature. 2017; 543(7647):681-686. PMC: 6246920. DOI: 10.1038/nature21408. View