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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MDPI AG
2023-02-01
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| Series: | Biomolecules |
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| author | Erfei Chen Fangfang Yang Qiqi Li Tong Li Danni Yao Lichao Cao Jin Yang |
| author_facet | Erfei Chen Fangfang Yang Qiqi Li Tong Li Danni Yao Lichao Cao Jin Yang |
| author_sort | Erfei Chen |
| collection | DOAJ |
| 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 <i>C9orf9</i>. The subsequent target sequencing of <i>C9orf9</i> 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. |
| first_indexed | 2024-03-11T09:06:17Z |
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| id | doaj.art-c2e82ac2aae54c2d99d85be50b48a268 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T09:06:17Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-c2e82ac2aae54c2d99d85be50b48a2682023-11-16T19:23:24ZengMDPI AGBiomolecules2218-273X2023-02-0113231210.3390/biom13020312Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal CancerErfei Chen0Fangfang Yang1Qiqi Li2Tong Li3Danni Yao4Lichao Cao5Jin Yang6Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, ChinaThe 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 <i>C9orf9</i>. The subsequent target sequencing of <i>C9orf9</i> 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.https://www.mdpi.com/2218-273X/13/2/312colorectal cancermetastasistumor suppressorepithelial mesenchymal transition |
| spellingShingle | Erfei Chen Fangfang Yang Qiqi Li Tong Li Danni Yao Lichao Cao Jin Yang Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer Biomolecules colorectal cancer metastasis tumor suppressor epithelial mesenchymal transition |
| 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 | colorectal cancer metastasis tumor suppressor epithelial mesenchymal transition |
| url | https://www.mdpi.com/2218-273X/13/2/312 |
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