Ritika Gangarapu

Introduction: Gastric Cancer is the third most common cause of cancer death worldwide, with over a million new cases each year¹. It is often caused by chronic inflammation of the gut mucosa through infection or consuming carcinogenic foods over time². One of the most common causes of gastric cancer is Helicobacter pylori (H. pylori), which was identified as a causative agent for roughly 89% of gastric cancers^2,3. Although a causative relationship between H. pylori and gastric cancer has already been established, the exact mechanisms for how H. pylori infection plays a role in the progression of gastric cancer has yet to be fully understood.  Methods and Results: To study the role that the pathogenic factor of H. pylori, cytotoxin-associated gene A (CagA), and Krüppel-like factor 4 (KLF4) have in the progression of gastric cancer, their relationships to two inflammatory mediators of gastric cancer, CXCL8 (IL-8) and microRNA (miR)-155, were analyzed. Immunohistochemistry showed that there was an inverse relationship between KLF4 and CXCL8 ⁴. KLF4 was shown to decrease expression of CXCL8 while CagA led to increased expression of CXCL8 by inhibiting KLF4 expression⁴. PCR results from gastric cancer cells and those infected with H. Pylori had higher rates of miR-155 expression as opposed to normal gastric epithelial cells⁵. TargetScan and a follow up luciferase assay showed that increased miR-155 expression resulted in decreased KLF4 expression⁵, suggesting that KLF4 was a target gene of miR-155. To confirm the role of miR-155 as an oncogene in gastric cancer, miR-155 was overexpressed or depleted in various gastric cancer cell lines⁵. The gastric cancer cells that had overexpression of miR-155 had downregulation of KLF4 and an increased epithelial to mesenchymal transition; the opposite occurred when miR-155 was inhibited, confirming the role of miR-155 as an oncogene in the progression of gastric cancer⁵. Conclusions: The current prognosis of gastric cancer is poor as treatments are limited¹. These studies demonstrated that KLF4 suppresses gastric cancer, suggesting that it can be a new therapeutic target for gastric cancer treatment. Understanding how CagA impacts KLF4 provides new insight for developing novel treatments of H. pylori associated gastric cancer.

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