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Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression
Colorectal cancer (CRC) is the third most common cancer worldwide. Here, we identified tumor-associated macrophages (TAMs) as regulators of genes in CRC. In total, the expressions of 457 genes were dysregulated after TAM coculture; specifically, 344 genes were up-regulated, and 113 genes were down-r...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849682/ https://www.ncbi.nlm.nih.gov/pubmed/33537240 http://dx.doi.org/10.3389/fonc.2020.618902 |
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author | Qi, Jingbo Hu, Zhiqiu Liu, Shaoqun Li, Fan Wang, Sheng Wang, Wuqing Sheng, Xia Feng, Li |
author_facet | Qi, Jingbo Hu, Zhiqiu Liu, Shaoqun Li, Fan Wang, Sheng Wang, Wuqing Sheng, Xia Feng, Li |
author_sort | Qi, Jingbo |
collection | PubMed |
description | Colorectal cancer (CRC) is the third most common cancer worldwide. Here, we identified tumor-associated macrophages (TAMs) as regulators of genes in CRC. In total, the expressions of 457 genes were dysregulated after TAM coculture; specifically, 344 genes were up-regulated, and 113 genes were down-regulated. Bioinformatic analysis implied that these TAM-related genes were associated with regulation of the processes of macromolecule metabolism, apoptosis, cell death, programmed cell death, and the response to stress. To further uncover the interplay among these proteins, we constructed a PPI network; 15 key regulators were identified in CRC, including VEGFA, FN1, JUN, CDH1, MAPK8, and FOS. Among the identified genes, we focused on PSMA2 and conducted loss-of-function experiments to validate the functions of PSMA2 in CRC. To further determine the mechanism by which PSMA2 affected CRC, we conducted multiple assays in CRC cell lines and tissues. PSMA2 enhanced the proliferation, migration and invasion of CRC cells. Moreover, our data indicated that PSMA2 expression was dramatically increased in stage 1, stage 2, stage 3, and stage 4 CRC samples. Our data indicated that PSMA2 was one target of miR-132. A miR-132 mimic greatly hindered CRC cell proliferation. In addition, the luciferase assay results revealed that miR-132 directly regulated PSMA2. Moreover, our data indicated that miR-132 expression was greatly decreased in CRC samples, which was associated with longer survival times of CRC patients, implying that miR-132 was a probable biomarker for CRC. Collectively, these data indicate that PSMA2 is a promising target for the therapy of CRC. |
format | Online Article Text |
id | pubmed-7849682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78496822021-02-02 Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression Qi, Jingbo Hu, Zhiqiu Liu, Shaoqun Li, Fan Wang, Sheng Wang, Wuqing Sheng, Xia Feng, Li Front Oncol Oncology Colorectal cancer (CRC) is the third most common cancer worldwide. Here, we identified tumor-associated macrophages (TAMs) as regulators of genes in CRC. In total, the expressions of 457 genes were dysregulated after TAM coculture; specifically, 344 genes were up-regulated, and 113 genes were down-regulated. Bioinformatic analysis implied that these TAM-related genes were associated with regulation of the processes of macromolecule metabolism, apoptosis, cell death, programmed cell death, and the response to stress. To further uncover the interplay among these proteins, we constructed a PPI network; 15 key regulators were identified in CRC, including VEGFA, FN1, JUN, CDH1, MAPK8, and FOS. Among the identified genes, we focused on PSMA2 and conducted loss-of-function experiments to validate the functions of PSMA2 in CRC. To further determine the mechanism by which PSMA2 affected CRC, we conducted multiple assays in CRC cell lines and tissues. PSMA2 enhanced the proliferation, migration and invasion of CRC cells. Moreover, our data indicated that PSMA2 expression was dramatically increased in stage 1, stage 2, stage 3, and stage 4 CRC samples. Our data indicated that PSMA2 was one target of miR-132. A miR-132 mimic greatly hindered CRC cell proliferation. In addition, the luciferase assay results revealed that miR-132 directly regulated PSMA2. Moreover, our data indicated that miR-132 expression was greatly decreased in CRC samples, which was associated with longer survival times of CRC patients, implying that miR-132 was a probable biomarker for CRC. Collectively, these data indicate that PSMA2 is a promising target for the therapy of CRC. Frontiers Media S.A. 2021-01-18 /pmc/articles/PMC7849682/ /pubmed/33537240 http://dx.doi.org/10.3389/fonc.2020.618902 Text en Copyright © 2021 Qi, Hu, Liu, Li, Wang, Wang, Sheng and Feng http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Qi, Jingbo Hu, Zhiqiu Liu, Shaoqun Li, Fan Wang, Sheng Wang, Wuqing Sheng, Xia Feng, Li Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression |
title | Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression |
title_full | Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression |
title_fullStr | Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression |
title_full_unstemmed | Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression |
title_short | Comprehensively Analyzed Macrophage-Regulated Genes Indicate That PSMA2 Promotes Colorectal Cancer Progression |
title_sort | comprehensively analyzed macrophage-regulated genes indicate that psma2 promotes colorectal cancer progression |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849682/ https://www.ncbi.nlm.nih.gov/pubmed/33537240 http://dx.doi.org/10.3389/fonc.2020.618902 |
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