An Overview on the Emerging Role of the Plasma Protease Inhibitor Protein ITIH5 as a Metastasis Suppressor.

Most cancers are not detected until they have progressed to the point of becoming malignant and life-threatening. Chemotherapy and conventional medicines are often ineffective against cancer. Although we have made significant progress, new conceptual discoveries are still required to investigate new treatments. The role of metastasis suppressor genes as a therapeutic option for limiting tumor progression and metastasis has been on the anvil for some time. In this review, we discuss the role of ITIH5 as a metastasis suppressor gene and catalog its involvement in different cancers. We further shed light on the mode of action of ITIH5 based on the available data. The review will provide a new perspective on ITIH5 as an anti-metastatic protein and hopefully serve as an impetus for future studies towards the application of ITIH5 for clinical intervention in targeting metastatic cancers.

HDAC inhibition regulates oxidative stress in CD4+Thelper cells of chronic obstructive pulmonary disease and non-small cell lung cancer patients via mitochondrial transcription factor a (mtTFA) modulating NF-κB/HIF1α axis.

Histone deacetylases (HDACs) play a crucial role in the epigenetic regulation of gene expression by remodelling chromatin. Isoenzymes of the HDAC family exhibit aberrant regulation in a wide variety of cancers as well as several inflammatory lung disorders like chronic obstructive pulmonary disease (COPD). Inhibition of HDACs is a potential therapeutic strategy that could be used to reverse epigenetic modification. Trichostatin A (TSA), a powerful histone deacetylase (HDAC) inhibitor, has anti-cancer effects in numerous cancer types. However, it is not yet apparent how HDAC inhibitors affect human non-small cell lung cancer cells (NSCLC) and COPD. This study aims to investigate TSA's role in restoring mitochondrial dysfunction and its effect on hypoxia and inflammation in CD4+T cells obtained from patients with COPD and lung cancer. As a result of treatment with TSA, there is a reduction in the expression of inflammatory cytokines and a decreased enrichment of transcriptional factors associated with inflammation at VEGFA gene loci. We have seen a substantial decrease in the expression of NF-κB and HIF1α, which are the critical mediators of inflammation and hypoxia, respectively. Following TSA treatment, mtTFA expression was increased, facilitating patients with COPD and NSCLC in the recovery of their dysfunctional mitochondria. Furthermore, we have discovered that TSA treatment in patients with COPD and NSCLC may lead to immunoprotective ness by inducing Th1ness. Our finding gives a new insight into the existing body of knowledge regarding TSA-based therapeutic methods and highlights the necessity of epigenetic therapy for these devastating lung disorders.