CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway

Purpose: Given the high incidence and mortality rates of colorectal cancer (CRC) and the inadequacy of existing treatments for many patients, this study aimed to explore the potential of Capping Actin Protein (CAPG), a protein involved in actin-related movements, as a novel therapeutic target for CR...

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Main Authors: Yingying Zhao, Rui Ma, Chuyue Wang, Rong Hu, Weili Wu, Xiang Sun, Baotao Chen, Wen Zhang, You Chen, Jiajian Zhou, Ping Yuan
Format: Article
Language:English
Published: Elsevier 2023-10-01
Series:Molecular and Cellular Probes
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0890850823000282
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author Yingying Zhao
Rui Ma
Chuyue Wang
Rong Hu
Weili Wu
Xiang Sun
Baotao Chen
Wen Zhang
You Chen
Jiajian Zhou
Ping Yuan
author_facet Yingying Zhao
Rui Ma
Chuyue Wang
Rong Hu
Weili Wu
Xiang Sun
Baotao Chen
Wen Zhang
You Chen
Jiajian Zhou
Ping Yuan
author_sort Yingying Zhao
collection DOAJ
description Purpose: Given the high incidence and mortality rates of colorectal cancer (CRC) and the inadequacy of existing treatments for many patients, this study aimed to explore the potential of Capping Actin Protein (CAPG), a protein involved in actin-related movements, as a novel therapeutic target for CRC. Methods: Bioinformatic analysis of gene expression was conducted using the UALCAN website. Cell proliferation was measured using the CCK-8 kit. Cell cycle, apoptosis, and ferroptosis were analyzed using flow cytometry. Tumorigenesis was evaluated by the subcutaneous inoculation of CRC cells into BALB/c nude female mice. Differentially expressed genes and signaling pathways were identified using RNA sequencing. Results: CAPG was significantly overexpressed in human CRC tissues and its upregulation was correlated with poor overall survival. CAPG knockdown led to notable inhibition of CRC cells in vitro and in vivo. Interference with CAPG blocked the cell cycle at the G1 phase and triggered apoptosis and ferroptosis by upregulating the P53 pathway in CRC cells. Conclusion: CRC patients with higher CAPG levels have a poorer prognosis. CAPG inhibits apoptosis and ferroptosis, while promoting CRC cell proliferation by repressing the P53 pathway. Our study suggests that CAPG may be a potential therapeutic target for CRC prognosis and treatment.
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spelling doaj.art-0e57c04ff86844d387dc7446e3a852752023-09-15T04:39:03ZengElsevierMolecular and Cellular Probes0890-85082023-10-0171101919CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathwayYingying Zhao0Rui Ma1Chuyue Wang2Rong Hu3Weili Wu4Xiang Sun5Baotao Chen6Wen Zhang7You Chen8Jiajian Zhou9Ping Yuan10Guangdong Institute of Gastroenterology, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Institute of Gastroenterology, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Institute of Gastroenterology, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Institute of Gastroenterology, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Institute of Gastroenterology, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, ChinaDermatology Hospital, Southern Medical University, Guangzhou, ChinaIQVIA Holding Inc, Beijing, ChinaGuangdong Institute of Gastroenterology, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDermatology Hospital, Southern Medical University, Guangzhou, ChinaGuangdong Institute of Gastroenterology, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Corresponding author. Guangdong Institute of Gastroenterology; Guangdong Provincial Key laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.Purpose: Given the high incidence and mortality rates of colorectal cancer (CRC) and the inadequacy of existing treatments for many patients, this study aimed to explore the potential of Capping Actin Protein (CAPG), a protein involved in actin-related movements, as a novel therapeutic target for CRC. Methods: Bioinformatic analysis of gene expression was conducted using the UALCAN website. Cell proliferation was measured using the CCK-8 kit. Cell cycle, apoptosis, and ferroptosis were analyzed using flow cytometry. Tumorigenesis was evaluated by the subcutaneous inoculation of CRC cells into BALB/c nude female mice. Differentially expressed genes and signaling pathways were identified using RNA sequencing. Results: CAPG was significantly overexpressed in human CRC tissues and its upregulation was correlated with poor overall survival. CAPG knockdown led to notable inhibition of CRC cells in vitro and in vivo. Interference with CAPG blocked the cell cycle at the G1 phase and triggered apoptosis and ferroptosis by upregulating the P53 pathway in CRC cells. Conclusion: CRC patients with higher CAPG levels have a poorer prognosis. CAPG inhibits apoptosis and ferroptosis, while promoting CRC cell proliferation by repressing the P53 pathway. Our study suggests that CAPG may be a potential therapeutic target for CRC prognosis and treatment.http://www.sciencedirect.com/science/article/pii/S0890850823000282CAPGCRCApoptosisP53Ferroptosis
spellingShingle Yingying Zhao
Rui Ma
Chuyue Wang
Rong Hu
Weili Wu
Xiang Sun
Baotao Chen
Wen Zhang
You Chen
Jiajian Zhou
Ping Yuan
CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway
Molecular and Cellular Probes
CAPG
CRC
Apoptosis
P53
Ferroptosis
title CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway
title_full CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway
title_fullStr CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway
title_full_unstemmed CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway
title_short CAPG interference induces apoptosis and ferroptosis in colorectal cancer cells through the P53 pathway
title_sort capg interference induces apoptosis and ferroptosis in colorectal cancer cells through the p53 pathway
topic CAPG
CRC
Apoptosis
P53
Ferroptosis
url http://www.sciencedirect.com/science/article/pii/S0890850823000282
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