A Novel Protein Encoded by Exosomal CircATG4B Induces Oxaliplatin Resistance in Colorectal Cancer by Promoting Autophagy

被引：85

作者：

Pan, Zihao ^{[1
,2
]}

Zheng, Jun ^{[3
,4
,5
]}

Zhang, Jiebin ^{[3
,4
,5
]}

Lin, Jiatong ^{[1
,6
]}

Lai, Jianguo ^{[7
]}

Lyu, Zejian ^{[1
,2
]}

Feng, Huolun ^{[1
,6
]}

Wang, Junjiang ^{[1
,2
]}

Wu, Deqing ^{[1
,2
]}

Li, Yong ^{[1
,2
]}

机构：

[1] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Gen Surg, Dept Gastrointestinal Surg, Guangzhou 510080, Peoples R China

[2] Southern Med Univ, Sch Clin Med 2, Guangzhou 510080, Peoples R China

[3] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Hepat Surg, Guangzhou 510630, Peoples R China

[4] Sun Yat Sen Univ, Affiliated Hosp 3, Liver Transplantat Ctr, Guangzhou 510630, Peoples R China

[5] Organ Transplantat Res Ctr Guangdong Prov, Guangdong Prov Engn Lab Transplantat Med, Guangzhou 510630, Peoples R China

[6] South China Univ Technol, Sch Med, Guangzhou 510006, Guangdong, Peoples R China

[7] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Canc Ctr, Dept Breast Canc, Guangzhou 510080, Peoples R China

来源：

ADVANCED SCIENCE | 2022年 / 9卷 / 35期

基金：

中国国家自然科学基金;

关键词：

autophagy; chemoresistance; circular RNA; colorectal cancer (CRC); CIRCULAR RNA; ATG4B; BIOMARKER;

D O I：

10.1002/advs.202204513

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Oxaliplatin is commonly used in chemotherapeutic regimens for colorectal cancer (CRC) after surgical resection. However, acquired chemoresistance seriously affects the curative effect in CRC patients, and the mechanism is still unclear. Here, a circular RNA, circATG4B is identified, which plays an important role in oxaliplatin resistance in CRC. circATG4B expression is found to be increased in exosomes secreted by oxaliplatin-resistant CRC cells. In addition, the results suggest that circATG4B induces oxaliplatin resistance by promoting autophagy. Further in vivo and in vitro studies indicate that the effect of circATG4B is attributed to its potential to encode a novel protein, circATG4B-222aa. Next, circATG4B-222aa is found to function as a decoy to competitively interact with TMED10 and prevent TMED10 from binding to ATG4B, which leads to increased autophagy followed by induction of chemoresistance. Therefore, this study reveals that exosomal circATG4B participates in the decreased chemosensitivity of CRC cells, providing a new rationale for a potential therapeutic target for oxaliplatin resistance in CRC.

引用

页数：16

共 53 条

[1] On ATG4B as Drug Target for Treatment of Solid Tumours-The Knowns and the Unknowns [J].

Agrotis, Alexander ;

Ketteler, Robin .

CELLS, 2020, 9 (01)

[2] Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis [J].

Cabrera, Sandra ;

Maciel, Mariana ;

Herrera, Iliana ;

Nava, Teresa ;

Vergara, Fabian ;

Gaxiola, Miguel ;

Lopez-Otin, Carlos ;

Selman, Moises ;

Pardo, Annie .

AUTOPHAGY, 2015, 11 (04) :670-684

[3] Targeting autophagy to overcome drug resistance: further developments [J].

Chang, Haocai ;

Zou, Zhengzhi .

JOURNAL OF HEMATOLOGY & ONCOLOGY, 2020, 13 (01)

[4] The Role of non-coding RNAs in colorectal cancer, with a focus on its autophagy [J].

Chen, Li ;

He, Man ;

Zhang, Meng ;

Sun, Qiang ;

Zeng, Sha ;

Zhao, Hui ;

Yang, Han ;

Liu, Maolun ;

Ren, Shan ;

Meng, Xianli ;

Xu, Haibo .

PHARMACOLOGY & THERAPEUTICS, 2021, 226

[5] The role of autophagy in targeted therapy for acute myeloid leukemia [J].

Du, Wenxin ;

Xu, Aixiao ;

Huang, Yunpeng ;

Cao, Ji ;

Zhu, Hong ;

Yang, Bo ;

Shao, Xuejing ;

He, Qiaojun ;

Ying, Meidan .

AUTOPHAGY, 2021, 17 (10) :2665-2679

[6] Circular RNA in Exosomes [J].

Fanale, Daniele ;

Taverna, Simona ;

Russo, Antonio ;

Bazan, Viviana .

CIRCULAR RNAS: BIOGENESIS AND FUNCTIONS, 2018, 1087 :109-117

[7] Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR-STAT3 signalling [J].

Gao, Xinya ;

Xia, Xin ;

Li, Fanying ;

Zhang, Maolei ;

Zhou, Huangkai ;

Wu, Xujia ;

Zhong, Jian ;

Zhao, Zheng ;

Zhao, Kun ;

Liu, Dawei ;

Xiao, Feizhe ;

Xu, Qiang ;

Jiang, Tao ;

Li, Bo ;

Cheng, Shi-Yuan ;

Zhang, Nu .

NATURE CELL BIOLOGY, 2021, 23 (03) :278-+

[8] Recruitment to Golgi membranes of ADP-ribosylation factor 1 is mediated by the cytoplasmic domain of p23 [J].

Gommel, DU ;

Memon, AR ;

Heiss, A ;

Lottspeich, F ;

Pfannstiel, J ;

Lechner, J ;

Reinhard, C ;

Helms, JB ;

Nickel, W ;

Wieland, FT .

EMBO JOURNAL, 2001, 20 (23) :6751-6760

[9] Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans [J].

Holdt, Lesca M. ;

Stahringer, Anika ;

Sass, Kristina ;

Pichler, Garwin ;

Kulak, Nils A. ;

Wilfert, Wolfgang ;

Kohlmaier, Alexander ;

Herbst, Andreas ;

Northoff, Bernd H. ;

Nicolaou, Alexandros ;

Gaebel, Gabor ;

Beutner, Frank ;

Scholz, Markus ;

Thiery, Joachim ;

Musunuru, Kiran ;

Krohn, Knut ;

Mann, Matthias ;

Teupser, Daniel .

NATURE COMMUNICATIONS, 2016, 7

[10] IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation [J].

Hu, Fuqing ;

Song, Da ;

Yan, Yumeng ;

Huang, Changsheng ;

Shen, Chentao ;

Lan, Jingqin ;

Chen, Yaqi ;

Liu, Anyi ;

Wu, Qi ;

Sun, Li ;

Xu, Feng ;

Hu, Fayong ;

Chen, Lisheng ;

Luo, Xuelai ;

Feng, Yongdong ;

Huang, Shengyou ;

Hu, Junbo ;

Wang, Guihua .

NATURE COMMUNICATIONS, 2021, 12 (01)

← 1 2 3 4 5 6 →