CRISPR-based knockout screening identifies the loss of MIEF2 to enhance oxaliplatin resistance in colorectal cancer through inhibiting the mitochondrial apoptosis pathway

作者全名："Xie, Chaozheng; Li, Kang; Li, Ya; Peng, Xudong; Teng, Biyun; He, Kuan; Jin, Aishun; Wang, Wang; Wei, Zhengqiang"

作者地址："[Xie, Chaozheng; Li, Ya; Peng, Xudong; He, Kuan; Wei, Zhengqiang] Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China; [Li, Kang] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing, Peoples R China; [Teng, Biyun] Chongqing Med Univ, Affiliated Hosp 1, Dept Vasc Surg, Chongqing, Peoples R China; [Jin, Aishun; Wang, Wang] Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immun, Chongqing, Peoples R China"

通信作者："Wei, ZQ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China.; Wang, W (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immun, Chongqing, Peoples R China."

来源：FRONTIERS IN ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000853645600001

JCR分区：Q2

影响因子：4.7

年份：2022

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：CRISPR screens; oxaliplatin; colorectal cancer; MIEF2; mitochondrial apoptosis

摘要："The first-line anticancer agent oxaliplatin (OXL) is the preferred drug for treating colorectal cancer (CRC); however, the development of drug resistance is common in patients treated with OXL, which considerably reduces the efficacy of OXL-based regimens. By performing genome-wide CRISPR/Cas9 library knockdown screening, we found that mitochondrial elongation factor 2 (MIEF2) was among the top candidate genes. The OXL-resistant cell lines and organoids developed in the present study showed stable but low expression of MIEF2. Reduced MIEF2 expression may enhance CRC resistance to OXL by reducing mitochondrial stability and inhibiting apoptosis by decreasing cytochrome C release. In conclusion, among the different biomarkers of OXL resistance in CRC, MIEF2 may serve as a specific biomarker of OXL responsiveness and a potential target for the development of therapies to improve chemotherapeutic effectiveness."

基金机构：Chongqing key diseases Research and Application Demonstration Program (Colorectal Cancer Prevention and Treatment Technology Research and Application Demonstration) [2019ZX003]; Chongqing Municipal Natural Science Foundation [cstc2018jcyjAX0194]; General project of Chongqing Nature Science Foundation [cstc2021jcyj-msxmX0283]

基金资助正文："This study was supported by Chongqing key diseases Research and Application Demonstration Program (Colorectal Cancer Prevention and Treatment Technology Research and Application Demonstration [No. 2019ZX003]), Chongqing Municipal Natural Science Foundation [No. cstc2018jcyjAX0194], and the General project of Chongqing Nature Science Foundation [No. cstc2021jcyj-msxmX0283]."