Cold Atmospheric Plasma Jet Irradiation Decreases the Survival and the Expression of Oncogenic miRNAs of Oral Carcinoma Cells

Abstract

Despite recent advancements, therapies against advanced oral squamous cell carcinoma (OSCC) remain ineffective, resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Although the effects of CAP in abrogating OSCC have been explored, the exact mechanisms driving CAP-induced cancer cell death and the changes in microRNA (miRNA) expression are not fully understood. We fabricated and calibrated an argon-CAP device to explore the effects of CAP irradiation on the growth and expression of oncogenic miRNAs in OSCC. The analysis revealed that, in OSCC cell lines following CAP irradiation, there was a significant reduction in viability; a downregulation of miR-21, miR-31, miR-134, miR-146a, and miR-211 expression; and an inactivation of the v-akt murine thymoma viral oncogene homolog (AKT) and extracellular signal-regulated kinase (ERK) signals. Pretreatment with blockers of apoptosis, autophagy, and ferroptosis synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways via CAP. Combined treatments using death inhibitors and miRNA mimics, alongside the activation of AKT and ERK following the exogenous expression, counteracted the cell mortality associated with CAP. The CAP-induced downregulation of miR-21, miR-31, miR-187, and miR-211 expression was rescued through survival signaling. Additionally, CAP irradiation notably inhibited the growth of SAS OSCC cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study provides new lines of evidence demonstrating that CAP irradiation diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy

“…Precision therapy is individualized pharmacological treatment based on specific characteristics of tumors ( 17 ). Tumor heterogeneity, variations in gene expression, and polymorphisms may all affect a patient’s response to medication differently.…”

“…Secondly, it is not possible to determine the appropriate CTC detection time. The morphological, genetic, and functional properties of CTCs differ due to various timeframes and treatment modalities, which impacts their therapeutic application ( 17 ). Therefore, the monitoring method for CTC is significantly challenged by its rarity and heterogeneity, which limits its clinical application to a certain extent.…”

“…The advantage of ctDNA is that it is widely and uniformly distributed in body fluids, and the standardization of detection techniques is relatively easy. However, like CTCs, tumor patients’ ctDNA content is extremely low, making missed detection possible and necessitating highly sensitive detection technology ( 17 ). After DNA amplification, it is now possible to directly, qualitatively and quantitatively examine ctDNA using well-established detection techniques such as NGS and digital PCR owing to the rapid improvement of DNA sequencing technology.…”

“…A potential novel approach to treating lung cancer may involve preventing the production and release of EVs. EVs can be employed for additional study of ctDNA and miRNA discovered in The stability of nucleic acid molecules is successfully maintained by EVs, protecting ctDNA from degradation ( 17 ). ExoDX Lung (ALK), the first cancer diagnosis product ever released by EVs Diagnostics, was introduced in 2016.…”

“…EVs contain cargoes of miRNAs,mRNAs, and proteins. It has been shown that microRNAs carried by EVs are associated with colorectal cancer ( 14 ), hepatocellular carcinoma ( 15 ), lung cancer ( 16 ), oral cancer ( 17 ), and ovarian cancer ( 18 ). The contents of EVs such as mRNA can promote epithelial-mesenchymal transition and chemoresistance in colorectal cancer ( 19 ).…”