Jovesh Zachariah

Introduction: Gastric cancer is the 5^th most common cancer worldwide.¹ Although there is a greater than 95% chance of 5-year survival if the disease is caught early enough due to recent advancements in radiotherapy and chemotherapy,² most patients die within 5 years of diagnosis because of how late the condition is usually detected.³ Symptoms include dyspepsia, heartburn, nausea, weight loss, and abdominal pain.⁴ However, symptoms are vague and generally do not occur until late in disease development.⁵ High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that is overexpressed in gastric cancer.⁶  HMGB1 functions as a chromatin-binding factor and bends DNA to give access to bind transcription factors that propagate cell growth.⁶ HMGB1 also contributes to the lymphangiogenesis of metastatic cancer through the activation of vascular endothelial growth factor C (VEGF-C).^7,8 MicroRNA’s are single stranded non-coding RNA’s that bind to the 3’ regions of untranslated mRNA and leads to their inactivation. MicroRNA-1179 targets HMGB1 and inhibits the proliferation and lymphangiogenesis of cells in gastric cancer.⁹ MicroRNA-129-5p also downregulates HGMB1 and impedes epithelial-mesenchymal transition in gastric cancer cells.¹⁰ The insights of these studies are promising and represent potential therapeutic applications in the treatment of gastric cancer. Methods: RT-qPCR analysis was used to identify the levels of mir-1179 in gastric cancer cells when contrasted with nearby healthy tissues.⁹ Cell lines that expressed diminished levels of miR-1179 were then transfected with miR-1179.⁹ Another RT-qPCR analysis of the expression level of miR-129-5p was done in gastric tissues.¹⁰ A HMGB1 inhibitor was transfected into cells and analyzed via western blot. Results: Lower miR-1179 expression was notably correlated with enhanced tumor size, higher tumor grade, as well as lymph node metastasis.⁹ Gastric cancer cells transfected with mir-1179 led to its overexpression and the downregulation of HMGB1.⁹ RT-qPCR analysis demonstrated that mir-129-5p was markedly down regulated in gastric cell lines when contrasted with normal cells.¹⁰ The western blot analysis of cells transfected with an HMGB1 inhibitor showed that the inhibition of HMGB1 led to the obstruction of the mesenchymal phenotype N-cadherin and propagation of E-cadherin, illustrating that the downregulation of HMGB1 led to epithelial-mesenchymal transition.¹⁰ Conclusions: The results show how microRNA-1179 binds to HMGB1 to impede the lymphangiogenesis and proliferation of gastric cancer. MicroRNA-129-5p also downregulates HMGB1 and prevents epithelial-mesenchymal transition. These represent potential therapeutic targets in the prevention of gastric cancer.

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