Mitochondrial protein isoleucyl-tRNA synthetase 2 in tumor cells as a potential therapeutic target for cervical cancer

Abstract

Objective: Isoleucyl-tRNA synthetase 2 (IARS2) is crucial for mitochondrial activity and function in cancer cells. Cervical cancer is a highly prevalent malignancy affecting the female reproductive system on a global scale. This research investigates the expression and potential roles of IARS2 in cervical cancer cells. Material and Methods: Initially, we examined the IARS2 expression profile in cervical cancer cells using Western blot technique and quantitative reverse transcription polymerase chain reaction methodologies. Subsequently, cervical cancer cell models with IARS2 silencing and overexpression were constructed using Short Hairpin RNA (ShRNA) (IARS2) and pcMV-FLAG-IARS2, respectively. The impact of IARS2 silencing or overexpression on Hela cell mitochondrial membrane potential, mitochondrial complex I, adenosine triphosphate (ATP) levels, reactive oxygen species activity, viability, proliferation, migration, apoptosis-related proteins, and apoptosis levels was examined through fluorescence staining, enzyme-linked immunosorbent assay, cell counting kit-8 assay, Transwell experiments, Western blot technique, and Terminal deoxynucleotidyl transferase dUTP nick end labeling assay techniques. Results: The expression of IARS2 is upregulated in cervical cancer cells. Silencing IARS2 with ShRNA (IARS2) disrupts mitochondrial function in cervical cancer cells, resulting in mitochondrial depolarization, heightened oxidative stress, suppression of mitochondrial complex I, and a decrease in ATP levels. Moreover, the depletion of IARS2 significantly impedes the viability, proliferation, and migration of cervical cancer cells, inducing apoptotic processes. In contrast, the overexpression of IARS2 augments the proliferation, migration, and ATP levels in cervical cancer cells. Conclusion: IARS2 plays a pivotal role as a mitochondrial protein in fostering the growth of cervical cancer cells, presenting itself as an innovative target for tumor diagnosis and treatment.