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ABSTRACT
Mitochondrial fission depends on dynamin-related protein 1 (Drp1) guanosine triphosphatase activity. Although there is some association between Drp1 and gastric cancer, the detailed mechanism remains largely unknown. In this study, the elevation of Drp1 was observed in human gastric carcinoma specimens including gastric mixed adenocarcinoma tissues, gastric intestinal-type adenocarcinoma tissues, and human gastric cancer cells compared to normal control, but not in diffuse gastric adenocarcinoma tissues. Gastric cancer patients with high Drp1 harbored advanced pathological stages and poor progression-free survival probability compared to those with low Drp1. Mdivi-1-mediated inactivation of Drp1 robustly inhibited cell viability and tumor growth but conversely induced cell apoptotic events in vitro and in vivo. Based on the Encyclopedia of RNA Interactomes Starbase, L22 ribosomal protein (RPL22) was recognized as the potential downstream oncogene of Drp1. Clinically, the significant correlation of Drp1 and RPL22 was also verified. Mechanistically, Drp1 inactivation did not affect the accumulation of RPL22 in gastric carcinoma. However, the intracellular distribution of RPL22 had an endonuclear location in Drp1-inactivated tumors. Of note, Drp1 inactivation notably reduced the expression of cytoplasmic RPL22 and increased its nuclear level in gastric cancer cells. Collectively, Drp1 had high levels in human gastric carcinoma specimens and could serve as a potential diagnostic and prognostic biomarker in gastric carcinoma. The Drp1 inactivation-mediated anti-proliferative and pro-apoptosis effects on gastric cancer were possibly associated with nuclear import of RPL22. This knowledge may provide new therapeutic tools for treating gastric carcinoma via targeting mitochondria-related ribosome pathway.
Acknowledgements
We thank the support of The Youth Innovation Team of Shaanxi Universities and Gene Expression Profiling Interactive Analysis 2.0 (GEPIA2).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Supplementary material
Supplemental data for this article can be accessed here
Author contributions
C.S. and G.X. conceived and designed the experiments; C.J. and C.S. performed the experiments; Z.R., G.J., S.Z., L.X. and C.P. analyzed the data; G.J., K.X., C.J. and R.K. contributed reagents and materials. All authors edited and approved the manuscript.
Ethics approval and consent to participate
All animal studies were approved according to institutional guidelines for laboratory animals. All experiments were approved by the ethics committee of Xi’an Medical University.
Abbreviations
Drp1, Dynamin-related protein 1; RPL22, L22 ribosomal protein; GEPIA2, Gene Expression Profiling Interactive Analysis 2; ENCORI, Encyclopedia of RNA Interactomes; ROS, reactive oxygen species; GTPases, guanosine triphosphatases; Mfn-2, mitofusin-2; mtDNA, mitochondrial DNAs; TCGA, The Cancer Genome Atlas.
