RESUMO
OBJECTIVES: Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. METHODS: We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. RESULTS: First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. CONCLUSION: Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Animais , Biomarcadores Tumorais , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico por imagem , Análise Serial de TecidosRESUMO
Immunotherapy has emerged as one of the most promising therapeutic strategies in cancer. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-Cas9) system, as an RNA-guided genome editing technology, is triggering a revolutionary change in cancer immunotherapy. With its versatility and ease of use, CRISPR-Cas9 can be implemented to fuel the production of therapeutic immune cells, such as construction of chimeric antigen receptor T (CAR-T) cells and programmed cell death protein 1 knockout. Therefore, CRISPR-Cas9 technology holds great promise in cancer immunotherapy. In this review, we will introduce the origin, development and mechanism of CRISPR-Cas9. Also, we will focus on its various applications in cancer immunotherapy, especially CAR-T cell-based immunotherapy, and discuss the potential challenges it faces.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Neoplasias/genética , Neoplasias/imunologia , Biomarcadores Tumorais , Terapia Genética , Humanos , Imunoterapia , Neoplasias/terapiaRESUMO
The imbalance of immune status in cancer microenvironment plays an important role in the development and progression of cancer. Immunotherapy based on this has become an important field of cancer research in recent years. Many studies on long noncoding RNA (lncRNA) in cancer have focus on its regulation in cancer development and metastasis. Recent studies have suggested that lncRNAs play crucial roles in different phases of cancer immunity, including antigen releasing, antigen presentation, immune activation, immune cells migration, infiltrating into cancer tissues, and killing cancer cells. The functional studies of lncRNAs in cancer immuntity revealed the complicated molecular mechanisms in cancer immunity from a new point of view, which may provide novel potential targets for cancer immunotherapies. Based on the classical cancer-immunity cycle theory, we review the recent studies on the functions and mechanisms of immune-related lncRNAs in different stages of cancer immunity, to summarize the relationship between lncRNAs, and cancer immunity and to provide a framework for further research.
Assuntos
Imunidade/genética , Imunidade/imunologia , Neoplasias/genética , Neoplasias/imunologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
Immunotherapies have emerged as the most promising area in cancer treatments in recent years. CD8+ T cells, as one of the primary effector cells of anticancer immunity, however, when infiltrating in cancer tissues, are generally in dysfunctional states termed T-cell exhaustion. Exhausted CD8+ T cells are characterized by impaired activity and proliferative ability, increased apoptotic rate and reduced production of effector cytokines. Such dysfunctional CD8+ T cells serve as a barrier in successful cancer elimination. Investigation on the mechanism of T-cell exhaustion was aiming to sustain or restore the efficiency of CD8+ T cells infiltrating in cancer, which may help to develop novel strategies to overcome cancer. Recent studies have found several vital mechanisms of CD8+ T-cell exhaustion and provided novel avenues through targeting CD8+ T-cell exhaustion to enhance anticancer immunity. Here, we review the recent progress in the study of CD8+ T-cell exhaustion to make a summary and to provide a framework for further researches.