POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration

被引：0

作者：

Xiao Yizhi ^{[1
,2
]}

Yang Ping ^{[1
]}

Xiao Wushuang ^{[1
]}

Yu Zhen ^{[1
]}

Li Jiaying ^{[1
]}

Li Xiaofeng ^{[2
]}

Lin Jianjiao ^{[3
,4
]}

Zhang Jieming ^{[1
]}

Pei Miaomiao ^{[1
]}

Hong Linjie ^{[1
]}

Yang Juanying ^{[1
]}

Lin Zhizhao ^{[1
]}

Jiang Ping ^{[1
]}

Xiang Li ^{[3
,4
]}

Li Guoxin ^{[5
]}

Ai Xinbo ^{[6
]}

Dai Weiyu ^{[1
,7
]}

Tang Weimei ^{[1
]}

Wang Jide ^{[1
,3
,4
]}

机构：

[1] Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

[2] Department of Gastroenterology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China

[3] Department of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen &amp

[4] Longgang District People’s Hospital of Shenzhen, Shenzhen, Guangdong, China

[5] Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

[6] Department of Gastroenterology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, Guangdong, China

[7] Department of Gastroenterology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong,

来源：

中华医学杂志英文版 | 2025年 / 138卷 / 07期

关键词：

Gastric cancer; POU2F1; miR-29b-3p; miR-29a-3p; Metastasis;

D O I：

暂无

中图分类号：

R735.2 [胃肿瘤];

学科分类号：

摘要：

Background: The transcription factorPOU2F1 regulates the expression levels of microRNAs in neoplasia. However, themiR-29b1/a cluster modulated byPOU2F1 in gastric cancer (GC) remains unknown.Methods: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNAin situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells.MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3′-UTR study were performed in GC cells.In vivo tumor metastasis was evaluated in nude mice.Results: POU2F1 is overexpressed in GC cell lines and binds to themiR-29b1/a cluster promoter.POU2F1 is upregulated, whereas maturemiR-29b-3p andmiR-29a-3p are downregulated in GC tissues.POU2F1 promotes GC metastasis by inhibitingmiR-29b-3p ormiR-29a-3p expressionin vitro andin vivo. Furthermore,PIK3R1 and/orPIK3R3 are direct targets ofmiR-29b-3p and/ormiR-29a-3p, and the ectopic expression ofPIK3R1 orPIK3R3 reverses the suppressive effect of maturemiR-29b-3p and/ormiR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction ofPIK3R1 withPIK3R3 promotes migration and invasion, andmiR-29b-3p,miR-29a-3p,PIK3R1, andPIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition,POU2F1,PIK3R1, andPIK3R3 expression levels negatively correlated withmiR-29b-3p andmiR-29a-3p expression levels in GC tissue samples.Conclusions: ThePOU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.

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