Exosomal circSHKBP1 participates in non-small cell lung cancer progression through PKM2-mediated glycolysis

被引：44

作者：

Chen, Wenbiao ^{[1
]}

Tang, Donge ^{[2
]}

Lin, Junqi ^{[1
]}

Huang, Xiaoming ^{[1
]}

Lin, Shaoming ^{[1
]}

Shen, Guanle ^{[1
]}

Dai, Yong ^{[2
]}

机构：

[1] Southern Med Univ, Peoples Hosp Longhua, Dept Resp Med, Affiliated Hosp, Jianshe East Rd, Shenzhen 518109, Peoples R China

[2] Southern Univ Sci & Technol, Shenzhen Peoples Hosp,Affiliated Hosp 1, Guangdong Prov Engn Res Ctr Autoimmune Dis Precis, Clin Med Res Ctr,Jinan Univ,Clin Med Coll 2, 1017 Dongmen North Rd, Shenzhen 518020, Peoples R China

来源：

MOLECULAR THERAPY ONCOLYTICS | 2022年 / 24卷

基金：

中国国家自然科学基金;

关键词：

CIRCULAR RNAS; NSCLC CELLS; KINASE M2; RESISTANCE; MACROPHAGE; PROMOTES;

D O I：

10.1016/j.omto.2022.01.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Non-small cell lung cancer (NSCLC) has a high morbidity and mortality, and it is imperative to explore the latent pathogenesis mechanism of NSCLC progression to find potential prognostic biomarkers and therapeutic targets. The present study aimed to explore the biological function of circSHKBP1 in NSCLC. circSHKBP1 was found to be upregulated in NSCLC tissues and cell lines and was enriched in exosomes derived from NSCLC cells. Exosomal circSHKBP1 enhanced the proliferation, migration, invasion, and stemness of NSCLC cells. miRNA-1294 was identified as a target for circSHKBP1, and circSHKBP1 upregulated PKM2 expression by sponging miR-1294. Exosomal circSHKBP1 regulated glycolysis through PKM2 in a HIF-1 alpha-dependent manner in NSCLC cells and promoted M2 polarization and macrophage recruitment. Moreover, exosomal circSHKBP1 promoted NSCLC cell growth, metastasis, and M2 infiltration in vivo. Thus, exosomal circSHKBP1 participated in the progression of NSCLC via the miR-1294/PKM2 axis. circSHKBP1 may be potential biomarker for the diagnosis and treatment of NSCLC.

引用

页码：470 / 485

页数：16

共 35 条

[1] FOXC1 induces cancer stem cell-like properties through upregulation of beta-catenin in NSCLC [J].

Cao, Sisi ;

Wang, Zhuo ;

Gao, Xiujuan ;

He, Wenjuan ;

Cai, Yue ;

Chen, Hui ;

Xu, Rong .

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2018, 37

[2] Regulation of circRNA biogenesis [J].

Chen, Ling-Ling ;

Yang, Li .

RNA BIOLOGY, 2015, 12 (04) :381-388

[3] ILT4 inhibition prevents TAM- and dysfunctional T cell-mediated immunosuppression and enhances the efficacy of anti-PD-L1 therapy in NSCLC with EGFR activation [J].

Chen, Xiaozheng ;

Gao, Aiqin ;

Zhang, Fang ;

Yang, Zijiang ;

Wang, Shuyun ;

Fang, Yuying ;

Li, Juan ;

Wang, Jingnan ;

Shi, Wenjing ;

Wang, Linlin ;

Zheng, Yan ;

Sun, Yuping .

THERANOSTICS, 2021, 11 (07) :3392-3416

[4] WIP1 promotes cancer stem cell properties by inhibiting p38 MAPK in NSCLC [J].

Deng, Kaiyuan ;

Liu, Liang ;

Tan, Xiaoming ;

Zhang, Zhen ;

Li, Jianjun ;

Ou, Yang ;

Wang, Xin ;

Yang, Shuang ;

Xiang, Rong ;

Sun, Peiqing .

SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2020, 5 (01)

[5] Exosomal Circ-MEMO1 Promotes the Progression and Aerobic Glycolysis of Non-small Cell Lung Cancer Through Targeting MiR-101-3p/KRAS Axis [J].

Ding, Chengzhi ;

Xi, Gaoyuan ;

Wang, Guolei ;

Cui, Dong ;

Zhang, Binbin ;

Wang, Hongtao ;

Jiang, Gongqian ;

Song, Jingchao ;

Xu, Guanghui ;

Wang, Jiao .

FRONTIERS IN GENETICS, 2020, 11

[6] Tumor-derived exosomes antagonize innate antiviral immunity [J].

Gao, Liang ;

Wang, Lin ;

Dai, Tong ;

Jin, Ke ;

Zhang, Zhengkui ;

Wang, Shuai ;

Xie, Feng ;

Fang, Pengfei ;

Yang, Bing ;

Huang, Huizhe ;

van Dam, Hans ;

Zhou, Fangfang ;

Zhang, Long .

NATURE IMMUNOLOGY, 2018, 19 (03) :233-+

[7] The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer (Publication with Expression of Concern. See vol. 16, 2025) [J].

Ge, Wan-Li ;

Chen, Qun ;

Meng, Ling-Dong ;

Huang, Xu-Min ;

Shi, Guo-dong ;

Zong, Qing-Qing ;

Shen, Peng ;

Lu, Yi-Chao ;

Zhang, Yi-Han ;

Miao, Yi ;

Zhang, Jing-Jing ;

Jiang, Kui-Rong .

CELL DEATH & DISEASE, 2020, 11 (04)

[8] Circular RNA and its mechanisms in disease: From the bench to the clinic [J].

Han, Bing ;

Chao, Jie ;

Yao, Honghong .

PHARMACOLOGY & THERAPEUTICS, 2018, 187 :31-44

[9] circ-SHKBP1 Regulates the Angiogenesis of U87 Glioma-Exposed Endothelial Cells through miR-544a/FOXP1 and miR-379/FOXP2 Pathways [J].

He, Qianru ;

Zhao, Lini ;

Liu, Yunhui ;

Liu, Xiaobai ;

Zheng, Jian ;

Yu, Hai ;

Cai, Heng ;

Ma, Jun ;

Liu, Libo ;

Wang, Ping ;

Li, Zhen ;

Xue, Yixue .

MOLECULAR THERAPY-NUCLEIC ACIDS, 2018, 10 :331-348

[10] Lung cancer: current therapies and new targeted treatments [J].

Hirsch, Fred R. ;

Scagliotti, Giorgio V. ;

Mulshine, James L. ;

Kwon, Regina ;

Curran, Walter J. ;

Wu, Yi-Long ;

Paz-Ares, Luis .

LANCET, 2017, 389 (10066) :299-311

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