Knockdown of Stromal Interaction Molecule 1 (STIM1) Suppresses Acute Myeloblastic Leukemia-M5 Cell Line Survival Through Inhibition of Reactive Oxygen Species Activities

Objective: This study aimed to investigate the role of the stromal interaction molecule 1 (STIM1) gene in the survival of the acute myeloblastic leukemia (AML)-M5 cell line (THP-1). Materials and Methods: The STIM1 effect was assessed via dicersubstrate siRNA-mediated STIM1 knockdown. The effect of STIM1 knockdown on the expression of AKT and MAPK pathway-related genes and reactive oxygen species (ROS) generation-related genes was tested using real-time polymerase chain reaction. Cellular functions, including ROS generation, cell proliferation, and colony formation, were also evaluated following STIM1 knockdown. Results: The findings revealed that STIM1 knockdown reduced intracellular ROS levels via downregulation of NOX2 and PKC. These findings were associated with the downregulation of AKT, KRAS, MAPK, and CMYC. BCL2 was also downregulated, while BAX was upregulated following STIM1 knockdown. Furthermore, STIM1 knockdown reduced THP-1 cell proliferation and colony formation. Conclusion: This study has demonstrated the role of STIM1 in promoting AML cell proliferation and survival through enhanced ROS generation and regulation of AKT/MAPK-related pathways. These findings may help establish STIM1 as a potential therapeutic target for AML treatment.

Racial Disparities Associated with the Prevalence of Vaccine and Non-Vaccine HPV Types and Multiple HPV Infections between Asia and Africa: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVE: Cervical Cancer is the 6th most common and 3rd most deadly cancer among women. Despite the fact that the majority of the countries in Asia and Africa have a similar economy and low life expectancy, the mean age-standardized incidence rate (ASIR) of cervical cancer is substantially higher in Africa than in Asia. This study identified the correlates of the higher ASIR rates in Africa relative to Asia against two timelines; 2004-2009 and 2010-2017. METHODS: Peer-reviewed articles published between 2004 and 2017 were selected using the PRISMA standard. Sources of articles included Google Scholar, Scopus, PubMed Central, and EMBASE. Search keywords included: HPV genotypes, cervical cancer, HPV vaccine, and multiple infections in Africa and Asia. RESULT: Twenty-nine and seventeen full-length articles were selected from Africa and Asia, respectively. The pooled prevalence of HPV infection up to 2017 was higher in Africa (41.8%; 95% CI: 35.9, 47.7) than in Asia (24.2%; 95% CI: 16.22, 32.2) at p< 0.001. Between 2004-2009 and 2010-2017 timelines, the pooled prevalence of HPV infection decreased from 49.1% to 36.7% (OR': 1.66, 95% CI: 1.51-1.80) in Africa and increased from 16.9% to 20.5% (OR': 0.79, 95% CI: 0.71-0.86) in Asia. However, the pooled prevalence of multiple HPV infections and non-vaccine high-risk HPV infections were higher among African women diagnosed with cancer (30.9% and 5.2%) than their Asian counterparts (21.0% and 2.0%, respectively) at p< 0.001. Additionally, the pooled prevalence of the five most prevalent high-risk HPV types in Africa were HPV16 (35.3%), HPV52 (14.2%), HPV35 (12.4%), HPV18 (10.4%), and HPV58 (10.0%), while that of Asia were HPV16 (37.3%), HPV52 (16.2%), HPV58 (14.7%), HPV33 (7.4%) and HPV18 (7.2%). CONCLUSION: This study suggests that the higher prevalence of HPV, multiple HPV and non-vaccine HPV infections could be responsible for the higher ASIR in Africa than in Asia.