Objective: To improve the prognosis of patients with gastric cancer (GC), more effective therapeutic targets are urgently needed. Increasing evidence indicates that miRNAs are involved in the progression of various tumors, and RAS-associated protein in the brain 31 (RAB31) is upregulated and promotes the progression of multiple malignant tumors. Here, we focused on identifying RAB31-targeted miRNAs and elucidating their potential mechanism in the progression of GC.Methods: RAB31 and miR-378a-3p expression levels were detected in paired fresh GC tissues and GC cell lines. Bioinformatics analysis was used to predict the miRNAs targeting RAB31 and the relationships between RAB31 and other genes. Dual-luciferase reporter assays were applied to verify the targeted interaction relationship. CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of GC cells. Tumorsphere formation assays were performed to assess the stemness of gastric cancer stem cells. Related proteins were detected by Western blot. Xenograft assays in nude mice were performed to explore the effect of miR-378a-3p in vivo. Results: We report the first evidence that miR-378a-3p is downregulated in GC, whereas its overexpression inhibits proliferation, invasion, and migration as well as promotes apoptosis in GC cells. Mechanistically, miR-378a-3p inhibits the progression of GC by directly targeting RAB31. Restoring RAB31 expression partially offsets the inhibitory effect of miR-378a-3p. Further research revealed that miR-378a-3p inhibits GLI1/2 in the Hedgehog signaling pathway and attenuates the stemness of gastric cancer stem cells. Finally, xenograft assays showed that miR-378a-3p inhibits GC tumorigenesis in vivo. Conclusions: MiR-378a-3p inhibits GC progression by directly targeting RAB31 and inhibiting the Hedgehog signaling pathway proteins GLI1/2.

Xinxin Xu;Yang Li;Guoxiao Liu;Kai Li;Peng Chen;Yunhe Gao;Wenquan Liang;Hongqing Xi;Xinxin Wang;Bo Wei;Hongtao Li;Lin Chen

Medical School of Chinese PLA,Beijing 100853,China;Senior Department of General Surgery,The First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Department of General Surgery,The 940th Hospital of Joint Logistics Support Force of People's Liberation Army,Lanzhou 730050,China

癌症生物学与医学（英文版）

[1]Xinxin Xu;Yang Li;Guoxiao Liu;Kai Li;Peng Chen;Yunhe Gao;Wenquan Liang;Hongqing Xi;Xinxin Wang;Bo Wei;Hongtao Li;Lin Chen-.MiR-378a-3p acts as a tumor suppressor in gastric cancer via directly targeting RAB31 and inhibiting the Hedgehog pathway proteins GLI1/2)[J].癌症生物学与医学（英文版）,2022(12):1662-1682

RAB31,Tumorsphere

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