RESUMO
Oral squamous cell carcinoma (OSCC) refers to the malignant tumor of the head and neck with a highest morbidity. It exhibits a poor prognosis and unsatisfactory treatment partially attributed to delayed diagnosis. As indicated from existing reports, the protein histidine phosphatase LHPP acts as a vital factor in tumorigenesis in liver, lung, bladder, breast and pancreatic tumor tissues. Thus far, the functional mechanism of LHPP in OSCC remains unclear. DGE analysis, OSCC cell lines and OSCC cases were found that LHPP was down-regulated in OSCC tissues and cells compared with that in normal oral mucosa tissues and cells, and was closely related to OSCC differentiation. Cell counting Kit 8 test, EdU proliferation test, scratches test, invasion test, monoclonal formation test, mouse xenograft tumor model, HE staining and immunohistochemistry showed that LHPP inhibited OSCC growth, proliferation and migration in vivo and in vitro. GO and KEGG enrichment analysis, LHPP transcription factor analysis and flow cytometry found that LHPP promotes the apoptosis of OSCC by decreasing the transcriptional activity of p-PI3K and p-Akt. Finally, our results suggested that LHPP inhibited the progression of OSCC through the PI3K/AKT signaling pathway, indicating that LHPP may be a new target for the treatment of OSCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Pirofosfatase Inorgânica/biossíntese , Neoplasias Bucais/metabolismo , Transdução de Sinais/fisiologia , Animais , Apoptose/fisiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Genes Supressores de Tumor , Humanos , Pirofosfatase Inorgânica/genética , Pirofosfatase Inorgânica/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The circadian clock refers to the intrinsic biological rhythms of physiological functions and behaviours. It synergises with the solar cycle and has profound effects on normal metabolism and organismal fitness. Recent studies have suggested that the circadian clock exerts great influence on the differentiation of stem cells. Here, we focus on the close relationship between the circadian clock and mesenchymal stem cell fate decisions in the skeletal system. The underlying mechanisms include hormone signals and the activation and repression of different transcription factors under circadian regulation. Additionally, the clock interacts with epigenetic modifiers and non-coding RNAs and is even involved in chromatin remodelling. Although the specificity and safety of circadian therapy need to be further studied, the circadian regulation of stem cells can be regarded as a promising candidate for health improvement and disease prevention.