RESUMO
OBJECTIVES: To investigate the upstream regulatory molecules of proteasomal activator 28γ (PA28γ), and explore its specific regulatory mechanism and potential clinical significance in OSCC. MATERIALS AND METHODS: qPCR was used to examine miR-34a, circFANCA and PSME3 expression. Western blotting was adopted to detect PA28γ expression. Transwell experiments were conducted to evaluate OSCC cell migration and invasion ability. FISH was used to evaluate the subcellular localization of circFANCA and miR-34a, and RNA pull-down verified the interaction between them. The expression of circFANCA and miR-34a in clinical cohorts was assessed by ISH, and the results were subjected to survival analysis using Kaplan-Meier analysis. RESULTS: Here, we proved that miR-34a expression is lower in highly aggressive OSCC tissues and cell lines. Notably, miR-34a can downregulate PA28γ expression and inhibit OSCC invasion and migration. Next, we confirmed that circFANCA promoted OSCC cell metastatic ability by sponging miR-34a. Importantly, interfering with miR-34a rescued the malignant progression of OSCC induced by silencing circFANCA. Finally, clinical data showed lower miR-34a expression and higher circFANCA expression were associated with poor prognosis in OSCC patients. CONCLUSION: The circFANCA/miR-34a/PA28γ axis facilitates the metastasis of OSCC, and circFANCA and miR-34a have potential to serve as prognostic markers for OSCC patients.
Assuntos
Carcinoma de Células Escamosas , MicroRNAs , Humanos , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de SinaisRESUMO
Ferroptosis is a newly defined form of regulated cell death (RCD) characterized by iron overload, lipid reactive oxygen species (ROS) accumulation, and lipid peroxidation, which is different from necrosis, apoptosis, autophagy and other forms of RCD in morphology, biochemistry, function and gene expression. Increasing evidence has shown that ferroptosis is intimately associated with cancer initiation, progression, and suppression. In this review, we summarize the primary mechanisms and signal pathways relevant to ferroptosis and then discuss the potential roles of ferroptosis in cancer, including those related to p53, noncoding RNA (ncRNA), and the tumor microenvironment (TME), to demonstrate the associations between ferroptosis and cancer. Moreover, we list some ferroptosis-based cancer therapies, such as clinical drugs, nanomaterials, exosomes and gene technology, based on previous studies. Finally, we propose some development avenues, challenges, and opportunities for further research on ferroptosis.
Assuntos
Ferroptose , Neoplasias/metabolismo , Exossomos , Humanos , Nanoestruturas , Neoplasias/genética , Neoplasias/terapia , RNA não Traduzido/fisiologia , Transdução de Sinais , Microambiente Tumoral , Proteína Supressora de Tumor p53/fisiologiaRESUMO
Photodynamic therapy (PDT) is a therapeutic modality that utilizes photodamage caused by photosensitizers and oxygen after exposure to a specific wavelength of light. Owing to its low toxicity, high selectivity, and minimally invasive properties, PDT has been widely applied to treat various malignant tumors, premalignant lesions, and infectious diseases. Moreover, there is growing evidence of its immunomodulatory effects and potential for the treatment of immune-related diseases. This review mainly focuses on the effect of PDT on immunity and its application in immune-related diseases.