Trend of disease burden and risk factors of breast cancer in developing countries and territories, from 1990 to 2019: Results from the Global Burden of Disease Study 2019

BackgroundThe incidence, mortality, burden of disability-adjusted life years (DALYs), and attributable risk factors of breast cancer vary significantly by country or region, particularly between developing and developed countries. This study aimed to analyze breast cancer development trends in developing countries based on the influence of the different sociodemographic indices (SDIs) and World Bank (WB) income-level disease data from 1990 to 2019.MethodsData on the annual incidence, mortality, DALY, years of life lost (YLL) prematurely, years lived with disability (YLD), and age-standardized rate (ASR) of breast cancer from 1990 to 2019 in different countries and territories were obtained from the 2019 Global Burden of Disease (GBD) Study. A comparative risk assessment (CRA) framework was used to analyze the general risk factors.ResultsThe global age-standardized incidence rate (ASIR) gradually increased from 21.44 per 100,000 population in 1990 to 24.17 per 100,000 population in 2019. It rose precipitously to 2.91- and 2.49-fold, respectively, for countries with middle SDIs and low-middle SDIs. The ASIR of breast cancer was increasing in the lower-middle-income levels in WB, with an estimated annual percentage change (EAPC) of 0.29 [95% uncertainty interval (UI): 0.20–0.37] and reduced income (EAPC of 0.59 [95% UI: 0.53–0.65]). The Solomon Islands and the United Arab Emirates observed the most significant increase in the magnitude of deaths from breast cancer cases. Compared to the death cases of 1990, percentage changes increased separately by 1,169 and 851%. Compared to developed areas, breast cancer-related deaths increased rapidly in developing regions, especially among the middle-aged and elderly groups. Meanwhile, the long-term burden of breast cancer was ever expanding. Of all the GBD regions, Oceania had the youngest age distribution. The deaths in the young and middle-aged groups accounted for 69% in 1990 and 72% in 2019. Percentage changes in deaths from the seven risk factors in low- to middle-SDI regions increased significantly over time across all age groups. However, a diet with high red meat and high body mass index (BMI) accounted for the most considerable increase in the magnitude.ConclusionPublic health policy regarding breast cancer is fundamental in low- and medium-income countries. The development and adoption of cost-effective screening and therapeutic solutions, the mitigation of risk factors, and the establishment of a cancer infrastructure are essential

SUMOylation of DEC1 Protein Regulates Its Transcriptional Activity and Enhances Its Stability

Differentiated embryo-chondrocyte expressed gene 1 (DEC1, also known as sharp2, stra13, or BHLHB2) is a mammalian basic helix-loop-helix protein that is involved in many aspects of gene regulation through acting as a transcription factor. Changes in DEC1 expression levels have been implicated in the development of cancers. Using COS-7 cell, we showed that DEC1 can be modified by the small ubiquitin-like modifiers, SUMO1, 2 and 3. Two major SUMOylation sites (K159 and K279) were identified in the C-terminal domain of DEC1. Substitution of either K159 or K279 with arginine reduced DEC1 SUMOylation, but substitution of both K159 and K279 abolished SUMOylation, and more protein appeared to be retained in the cytoplasm compared to wild-type DEC1. The expression of DEC1 was up-regulated after serum starvation as previously reported, but at the same time, serum starvation also led to more SUMOylation of DEC1. In MCF-7 cells SUMOylation also stabilized DEC1 through inhibiting its ubiquitination. Moreover, SUMOylation of DEC1 promoted its repression of CLOCK/BMAL1-mediated transcriptional activity through recruitment of histone deacetylase1. These findings suggested that posttranslational modification of DEC1 in the form of SUMOylation may serve as a key factor that regulates the function of DEC1 in vivo

Ubiquitination-Proteasome System (UPS) and Autophagy Two Main Protein Degradation Machineries in Response to Cell Stress

In response to environmental stimuli, cells make a series of adaptive changes to combat the injury, repair the damage, and increase the tolerance to the stress. However, once the damage is too serious to repair, the cells will undergo apoptosis to protect the overall cells through suicidal behavior. Upon external stimulation, some intracellular proteins turn into unfolded or misfolded protein, exposing their hydrophobic regions to form protein aggregation, which may ultimately produce serious damage to the cells. Ubiquitin plays an important role in the degradation of these unnatural proteins by tagging with ubiquitin chains in the ubiquitin–proteasome or autophagy system. If the two processes fail to eliminate the abnormal protein aggregates, the cells will move to apoptosis and death. Dysregulation of ubiquitin–proteasome system (UPS) and autophagy may result in the development of numerous diseases. This review focuses on the molecular mechanisms of UPS and autophagy in clearance of intracellular protein aggregates, and the relationship between dysregulation of ubiquitin network and diseases

The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells

Small ubiquitin-like modifier (SUMO)ylation is a reversible post-translational modification that plays a crucial role in numerous aspects of cell physiology, including cell cycle regulation, DNA damage repair, and protein trafficking and turnover, which are of importance for cell homeostasis. Mechanistically, SUMOylation is a sequential multi-enzymatic process where SUMO E3 ligases recruit substrates and accelerate the transfer of SUMO onto targets, modulating their interactions, localization, activity, or stability. Accumulating evidence highlights the critical role of dysregulated SUMO E3 ligases in processes associated with the occurrence and development of cancers. In the present review, we summarize the SUMO E3 ligases, in particular, the novel ones recently identified, and discuss their regulatory roles in cancer pathogenesis

The Role of PPARs in Breast Cancer

Breast cancer is a malignant tumor with high morbidity and lethality. Its pathogenesis is related to the abnormal expression of many genes. The peroxisome proliferator-activated receptors (PPARs) are a class of ligand-dependent transcription factors in the nuclear receptor superfamily. They can regulate the transcription of a large number of target genes, which are involved in life activities such as cell proliferation, differentiation, metabolism, and apoptosis, and regulate physiological processes such as glucose metabolism, lipid metabolism, inflammation, and wound healing. Further, the changes in its expression are associated with various diseases, including breast cancer. The experimental reports related to “PPAR” and “breast cancer” were retrieved from PubMed since the discovery of PPARs and summarized in this paper. This review (1) analyzed the roles and potential molecular mechanisms of non-coordinated and ligand-activated subtypes of PPARs in breast cancer progression; (2) discussed the correlations between PPARs and estrogen receptors (ERs) as the nuclear receptor superfamily; and (3) investigated the interaction between PPARs and key regulators in several signaling pathways. As a result, this paper identifies PPARs as targets for breast cancer prevention and treatment in order to provide more evidence for the synthesis of new drugs targeting PPARs or the search for new drug combination treatments

The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells

Small ubiquitin-like modifier (SUMO)ylation is a reversible post-translational modification that plays a crucial role in numerous aspects of cell physiology, including cell cycle regulation, DNA damage repair, and protein trafficking and turnover, which are of importance for cell homeostasis. Mechanistically, SUMOylation is a sequential multi-enzymatic process where SUMO E3 ligases recruit substrates and accelerate the transfer of SUMO onto targets, modulating their interactions, localization, activity, or stability. Accumulating evidence highlights the critical role of dysregulated SUMO E3 ligases in processes associated with the occurrence and development of cancers. In the present review, we summarize the SUMO E3 ligases, in particular, the novel ones recently identified, and discuss their regulatory roles in cancer pathogenesis

The Role of PPARs in Breast Cancer

Breast cancer is a malignant tumor with high morbidity and lethality. Its pathogenesis is related to the abnormal expression of many genes. The peroxisome proliferator-activated receptors (PPARs) are a class of ligand-dependent transcription factors in the nuclear receptor superfamily. They can regulate the transcription of a large number of target genes, which are involved in life activities such as cell proliferation, differentiation, metabolism, and apoptosis, and regulate physiological processes such as glucose metabolism, lipid metabolism, inflammation, and wound healing. Further, the changes in its expression are associated with various diseases, including breast cancer. The experimental reports related to “PPAR” and “breast cancer” were retrieved from PubMed since the discovery of PPARs and summarized in this paper. This review (1) analyzed the roles and potential molecular mechanisms of non-coordinated and ligand-activated subtypes of PPARs in breast cancer progression; (2) discussed the correlations between PPARs and estrogen receptors (ERs) as the nuclear receptor superfamily; and (3) investigated the interaction between PPARs and key regulators in several signaling pathways. As a result, this paper identifies PPARs as targets for breast cancer prevention and treatment in order to provide more evidence for the synthesis of new drugs targeting PPARs or the search for new drug combination treatments