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SPIN1 promotes the migration and invasion of gastric adenocarcinoma cells by activating the JAK2/STAT3 pathway
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Abstract:
[Abstract] Objective: To explore the molecular mechanism of spindlin1 (SPIN1) in promoting the migration and invasion of gastric adenocarcinoma cells. Methods: The correlations between SPIN1 mRNA expression and epithelial-mesenchymal transition (EMT) score and angiogenesis fraction in gastric adenocarcinoma tissues were analyzed by TCGA database. Tissue microarrays were constructed from a total of 52 surgically resected gastric adenocarcinoma specimens collected in Affiliated Provincial Hospital of Shandong First Medical University between August 2018 and November 2021. Each case included matched samples of gastric adenocarcinoma tissue, adjacent non?tumor tissue, and lymph node metastasis. The expression levels and correlation of SPIN1 and STAT3 in the gastric adenocarcinoma tissue samples were subsequently detected using immunohistochemistry. The effect of interfering with SPIN1 on the invasion and migration of gastric adenocarcinoma cells was investigated by Transwell chamber experiment. The GEPIA2 website was used to analyze the expression correlation between the SPIN1 gene and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway-related factor in gastric adenocarcinoma. Subsequently, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were employed to detect changes in the expression levels of JAK/STAT pathway-related mRNAs and proteins following SPIN1 interference. Results: Analysis of TCGA data showed that SPIN1 expression was positively correlated with both EMT and angiogenesis scores (both P < 0.05). Elevated expressions of SPIN1 and STAT3 were observed in gastric adenocarcinoma tissues and lymph node metastases (both P < 0.05) while they were negatively expressed in adjacent gastric mucosal tissues. A statistically significant positive correlation was found between SPIN1 and STAT3 expression (P < 0.05). Knockdown of SPIN1 significantly reduced the migratory and invasive capacities of gastric adenocarcinoma cells (P < 0.05 or P < 0.01). Furthermore, GEPIA2 analysis demonstrated significant positive correlations between the SPIN1 gene and the expression levels of JAK1, JAK2, STAT1, STAT2, and STAT3 (all P < 0.05). SPIN1 interference specifically reduced mRNA expressions of JAK2 and STAT3, while no significant changes were detected in JAK1, STAT1, or STAT2 mRNA levels. Western blotting confirmed that SPIN1 knockdown significantly decreased protein expression levels of JAK2, STAT3, phosphorylated JAK2 (p-JAK2), and phosphorylated STAT3 (p-STAT3) (all P < 0.01), whereas SPIN1 overexpression significantly upregulated the expressions of these proteins (all P < 0.01). Conclusion: SPIN1 can promote the migration and invasion of gastric adenocarcinoma cells by participating in the JAK2/STAT3 signaling pathway.
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