POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration
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 ch...
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| Language: | English |
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Wolters Kluwer
2025-04-01
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| Series: | Chinese Medical Journal |
| Online Access: | http://journals.lww.com/10.1097/CM9.0000000000003181 |
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| author | Yizhi Xiao Ping Yang Wushuang Xiao Zhen Yu Jiaying Li Xiaofeng Li Jianjiao Lin Jieming Zhang Miaomiao Pei Linjie Hong Juanying Yang Zhizhao Lin Ping Jiang Li Xiang Guoxin Li Xinbo Ai Weiyu Dai Weimei Tang Jide Wang Yanjie Yin |
| author_facet | Yizhi Xiao Ping Yang Wushuang Xiao Zhen Yu Jiaying Li Xiaofeng Li Jianjiao Lin Jieming Zhang Miaomiao Pei Linjie Hong Juanying Yang Zhizhao Lin Ping Jiang Li Xiang Guoxin Li Xinbo Ai Weiyu Dai Weimei Tang Jide Wang Yanjie Yin |
| author_sort | Yizhi Xiao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5be59f2b3be04f628bfabcd04744db21 |
| institution | OA Journals |
| issn | 0366-6999 2542-5641 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wolters Kluwer |
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| series | Chinese Medical Journal |
| spelling | doaj-art-5be59f2b3be04f628bfabcd04744db212025-08-20T02:25:43ZengWolters KluwerChinese Medical Journal0366-69992542-56412025-04-01138783885010.1097/CM9.0000000000003181202504050-00008POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migrationYizhi Xiao0Ping Yang1Wushuang Xiao2Zhen Yu3Jiaying Li4Xiaofeng Li5Jianjiao Lin6Jieming Zhang7Miaomiao Pei8Linjie Hong9Juanying Yang10Zhizhao Lin11Ping Jiang12Li Xiang13Guoxin Li14Xinbo Ai15Weiyu Dai16Weimei Tang17Jide Wang18Yanjie Yin1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China2 Department of Gastroenterology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China3 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, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China3 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, China4 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China5 Department of Gastroenterology, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, Guangdong 519000, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China1 Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaAbstract. 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.http://journals.lww.com/10.1097/CM9.0000000000003181 |
| spellingShingle | Yizhi Xiao Ping Yang Wushuang Xiao Zhen Yu Jiaying Li Xiaofeng Li Jianjiao Lin Jieming Zhang Miaomiao Pei Linjie Hong Juanying Yang Zhizhao Lin Ping Jiang Li Xiang Guoxin Li Xinbo Ai Weiyu Dai Weimei Tang Jide Wang Yanjie Yin POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration Chinese Medical Journal |
| title | POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration |
| title_full | POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration |
| title_fullStr | POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration |
| title_full_unstemmed | POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration |
| title_short | POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration |
| title_sort | pou2f1 inhibits mir 29b1 a cluster mediated suppression of pik3r1 and pik3r3 expression to regulate gastric cancer cell invasion and migration |
| url | http://journals.lww.com/10.1097/CM9.0000000000003181 |
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