SEMA3B-AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B-dependent VEGF signaling pathway activation
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Updated: Jul 16, 2025

Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma
Published on: September 3, 2021
Yi-Qing Wang1,2, Hui Chen1,2, Shuang Xu1,2
1Department of Pathology Nanfang Hospital Southern Medical University Guangzhou Guangdong China.
Abstract:
Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B-AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B-AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B-AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B-AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B-AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B-AS1 promoted the expression of its sense-cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B-AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B-NRP1 axis. Our work unravels a novel mechanism of SEMA3B-AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.
Insights
Long noncoding RNA SEMA3B-AS1 is downregulated in colorectal cancer (CRC), suppressing tumor growth and metastasis. This lncRNA holds potential as a diagnostic marker and therapeutic target for CRC.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) play critical roles in cancer development.
- LncRNA SEMA3B-AS1 is dysregulated in some cancers, but its role in colorectal cancer (CRC) is unknown.
Purpose of the Study:
- To investigate the function and mechanism of lncRNA SEMA3B-AS1 in colorectal cancer (CRC) progression.
Main Methods:
- Analysis of SEMA3B-AS1 expression in CRC tissues and cell lines.
- In vitro and in vivo experiments to assess the effects of SEMA3B-AS1 overexpression on CRC cell growth and metastasis.
- Mechanistic studies involving gene expression, protein interactions, and epigenetic modifications (H3K9 acetylation).
- Investigation of the SEMA3B-NRP1 axis and its role in CRC angiogenesis.
Main Results:
- SEMA3B-AS1 expression was significantly downregulated in CRC tissues and cell lines.
- Lower SEMA3B-AS1 levels correlated with poor patient survival.
- Overexpression of SEMA3B-AS1 inhibited CRC cell proliferation and metastasis.
- SEMA3B-AS1 epigenetically upregulated its sense gene SEMA3B by recruiting EP300.
- SEMA3B-AS1 suppressed CRC angiogenesis via the SEMA3B-NRP1 axis and vascular endothelial growth factor signaling.
Conclusions:
- SEMA3B-AS1 acts as a tumor suppressor in colorectal cancer.
- SEMA3B-AS1 inhibits CRC progression by regulating SEMA3B expression and angiogenesis.
- SEMA3B-AS1 represents a potential diagnostic biomarker and therapeutic target for CRC.
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