Exosome-Derived Circ_0094343 Promotes Chemosensitivity of Colorectal Cancer Cells by Regulating Glycolysis via the miR-766-5p/TRIM67 Axis

Author:

Li Chen12,Li Xu134ORCID

Affiliation:

1. Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi 710061, China

2. Molecular Testing Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121011, China

3. Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

4. Key Laboratory of Environment and Genes Related to Diseases (Xi’an Jiaotong University), Ministry of Education of China, Xi’an, China

Abstract

Objective. Currently, the role of circ_0094343 (circPTEN) on the chemosensitivity of CRC remains to be clarified. This study aimed to investigate the role and mechanism of exosome-delivered circ_0094343 in the proliferation, glycolysis, and chemosensitivity of colorectal cancer (CRC) cells. Methods. Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to detect the expression level of circ_0094343, miR-766-5p, and TRIM67 (Tripartite motif-containing 67) in CRC clinical tissue samples and cells, transmission electron microscopy (TEM) to observe the morphology of exosomes, and nanoparticle tracking analysis (NTA) system to measure the diameter of exosomes. Besides, PKH67 fluorescent labeling was applied for assessing the level of exosome uptake by cells, MTT and cell clone formation assays for detecting cell proliferation and clone formation, respectively, and related kits for checking the glucose consumption, lactate production, and extracellular acidification rate (ECAR) in cells. Dual-luciferase reporter (DLR) gene assay was used for verifying the targeting relationship between circ_0094343 and miR-766-5p, miR-766-5p and TRIM67, RNA immunoprecipitation (RIP) experiment for the interaction between circ_0094343 and miR-766-5p, and Western blot for the protein level of exosome surface antigens (HSP70, CD63) and TRIM67 in cells in exosomes and cell lysates. Results. circ_0094343 was significantly downregulated in CRC tissues, chemotherapy-resistant CRC tissues, and metastatic CRC tissues. Moreover, exosomes-carried circ_0094343 played an inhibitory role in the proliferation, clone formation and glycolysis of HCT116 cells. Meanwhile, it could also improve the chemosensitivity of HCT116 cells to 5-fluorouracil (5-FU), oxaliplatin (L-OHP), and doxorubicin (Dox). Additionally, circ_0094343 acted as a sponge for miR-766-5p, and miR-766-5p targeted and regulated TRIM67. In CRC tissues, miR-766-5p expression was negatively correlated with TRIM67 expression, while circ_0094343 was positively associated with TRIM67. Further, mechanistic validation also demonstrated that circ_0094343 could inhibit HCT116 cell proliferation, clone formation, glycolysis, and chemotherapy resistance via the miR-766-5p/TRIM67 axis. Conclusion. circ_0094343 inhibited the proliferation, clone formation and glycolysis of CRC cells and improved their chemosensitivity to various chemotherapeutic drugs via the miR-766-5p/TRIM67 axis. This finding may provide new insights into the treatment of CRC.

Funder

Department of Education of Liaoning Province

Publisher

Hindawi Limited

Subject

Radiology, Nuclear Medicine and imaging

Cited by 23 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3