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Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer

The whole genome sequencing of tumor samples identifies thousands of somatic mutations. However, the function of these genes or mutations in regulating cancer progression remains unclear. We previously performed exome sequencing in patients with colorectal cancer, and identified one splicing mutatio...

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Autores principales: Chen, Erfei, Yang, Fangfang, Li, Qiqi, Li, Tong, Yao, Danni, Cao, Lichao, Yang, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953698/
https://www.ncbi.nlm.nih.gov/pubmed/36830681
http://dx.doi.org/10.3390/biom13020312
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author Chen, Erfei
Yang, Fangfang
Li, Qiqi
Li, Tong
Yao, Danni
Cao, Lichao
Yang, Jin
author_facet Chen, Erfei
Yang, Fangfang
Li, Qiqi
Li, Tong
Yao, Danni
Cao, Lichao
Yang, Jin
author_sort Chen, Erfei
collection PubMed
description The whole genome sequencing of tumor samples identifies thousands of somatic mutations. However, the function of these genes or mutations in regulating cancer progression remains unclear. We previously performed exome sequencing in patients with colorectal cancer, and identified one splicing mutation in C9orf9. The subsequent target sequencing of C9orf9 gene based on a validation cohort of 50 samples also found two function mutations, indicating that the loss of wild-type C9orf9 may participate in the tumorigenesis of colorectal cancer. In this research, we aimed to further confirm the function of C9orf9 in the CRC phenotype. Our Q-PCR analysis of the tumor and matched normal samples found that C9orf9 was downregulated in the CRC samples. Function assays revealed that C9orf9 exerts its tumor suppressor role mainly on cancer cell migration and invasion, and its loss was essential for certain tumor-microenvironment signals to induce EMT and metastasis in vivo. RNA-sequencing showed that stable-expressing C9orf9 can inhibit the expression of several metastasis-related genes and pathways, including vascular endothelial growth factor A (VEGFA), one of the essential endothelial cell mitogens which plays a critical role in normal physiological and tumor angiogenesis. Overall, our results showed that the loss of C9orf9 contributes to the malignant phenotype of CRC. C9orf9 may serve as a novel metastasis repressor for CRC.
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spelling pubmed-99536982023-02-25 Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer Chen, Erfei Yang, Fangfang Li, Qiqi Li, Tong Yao, Danni Cao, Lichao Yang, Jin Biomolecules Article The whole genome sequencing of tumor samples identifies thousands of somatic mutations. However, the function of these genes or mutations in regulating cancer progression remains unclear. We previously performed exome sequencing in patients with colorectal cancer, and identified one splicing mutation in C9orf9. The subsequent target sequencing of C9orf9 gene based on a validation cohort of 50 samples also found two function mutations, indicating that the loss of wild-type C9orf9 may participate in the tumorigenesis of colorectal cancer. In this research, we aimed to further confirm the function of C9orf9 in the CRC phenotype. Our Q-PCR analysis of the tumor and matched normal samples found that C9orf9 was downregulated in the CRC samples. Function assays revealed that C9orf9 exerts its tumor suppressor role mainly on cancer cell migration and invasion, and its loss was essential for certain tumor-microenvironment signals to induce EMT and metastasis in vivo. RNA-sequencing showed that stable-expressing C9orf9 can inhibit the expression of several metastasis-related genes and pathways, including vascular endothelial growth factor A (VEGFA), one of the essential endothelial cell mitogens which plays a critical role in normal physiological and tumor angiogenesis. Overall, our results showed that the loss of C9orf9 contributes to the malignant phenotype of CRC. C9orf9 may serve as a novel metastasis repressor for CRC. MDPI 2023-02-07 /pmc/articles/PMC9953698/ /pubmed/36830681 http://dx.doi.org/10.3390/biom13020312 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Erfei
Yang, Fangfang
Li, Qiqi
Li, Tong
Yao, Danni
Cao, Lichao
Yang, Jin
Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer
title Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer
title_full Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer
title_fullStr Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer
title_full_unstemmed Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer
title_short Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer
title_sort loss of tumor suppressor c9orf9 promotes metastasis in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953698/
https://www.ncbi.nlm.nih.gov/pubmed/36830681
http://dx.doi.org/10.3390/biom13020312
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