POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration.
10.1097/CM9.0000000000003181
- Author:
Yizhi XIAO
1
;
Ping YANG
1
;
Wushuang XIAO
1
;
Zhen YU
1
;
Jiaying LI
1
;
Xiaofeng LI
2
;
Jianjiao LIN
3
;
Jieming ZHANG
1
;
Miaomiao PEI
1
;
Linjie HONG
1
;
Juanying YANG
1
;
Zhizhao LIN
1
;
Ping JIANG
1
;
Li XIANG
3
;
Guoxin LI
4
;
Xinbo AI
5
;
Weiyu DAI
1
;
Weimei TANG
1
;
Jide WANG
1
Author Information
1. Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
2. Department of Gastroenterology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China.
3. Department of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong 518172, China.
4. Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
5. Department of Gastroenterology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, Guangdong 519000, China.
- Publication Type:Journal Article
- Keywords:
Gastric cancer;
Metastasis
- MeSH:
MicroRNAs/metabolism*;
Humans;
Stomach Neoplasms/pathology*;
Cell Line, Tumor;
Cell Movement/physiology*;
Phosphatidylinositol 3-Kinases/metabolism*;
Animals;
Mice;
Octamer Transcription Factor-1/metabolism*;
Mice, Nude;
Class Ia Phosphatidylinositol 3-Kinase/metabolism*;
Neoplasm Invasiveness;
Gene Expression Regulation, Neoplastic/genetics*;
Male;
Immunohistochemistry;
Female
- From:
Chinese Medical Journal
2025;138(7):838-850
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 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 RNA in 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 the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 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 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples.
CONCLUSIONS:The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
