Exosomal lncRNA Mir100hg derived from cancer stem cells enhance glycolysis and promote metastasis of lung adenocarcinoma through mircroRNA-15a-5p/31-5p

Lei Shi; Bowen Li; Yuhan Zhang; Yuting Chen; Jiyu Tan; Yan Chen; Jie Li; Meng Xiang; H Rosie Xing; Jianyu Wang

doi:10.1186/s12964-023-01281-3

Exosomal lncRNA Mir100hg derived from cancer stem cells enhance glycolysis and promote metastasis of lung adenocarcinoma through mircroRNA-15a-5p/31-5p

Cell Commun Signal. 2023 Sep 21;21(1):248. doi: 10.1186/s12964-023-01281-3.

Authors

Lei Shi^#^{1

2}, Bowen Li^#^{1

2}, Yuhan Zhang^{1

2}, Yuting Chen^{1

2}, Jiyu Tan^{1

2}, Yan Chen^{1

2}, Jie Li³, Meng Xiang^{1

2}, H Rosie Xing^{4

5}, Jianyu Wang⁶

Affiliations

¹ State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China.
² Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China.
³ Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China.
⁴ State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China. 102643@cqmu.edu.cn.
⁵ Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, China. 102643@cqmu.edu.cn.
⁶ Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China. 102758@cqmu.edu.cn.

^# Contributed equally.

Abstract

Background: Exosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions between tumor cells and other cell populations in the tumor microenvironment have attracted most attention, little is known about the significance of exosomes in mediating the interaction between non-stemness cancer cells and cancer stem cells during cancer progression.

Methods: The structure, sequence and downstream target miRNAs of lncRNA Mir100hg were predicted by online web resources. The bioinformatics prediction results were validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing and mouse tail vein model of pulmonary metastasis. A complex regulatory network of "cancer stem cells-exosomal lncRNA-non-stem cancer cells" was constructed.

Results: This study demonstrates firstly that lncRNA Mir100hg is upregulated in lung cancer stem cell LLC-SD (Lung cancer stem cells) and can be delivered to non-stemness cancer cells LLC (Lewis lung cancer cells) via exosomes. In LLC, Mir100hg targets miR-15a-5p and miR-31-5p which leads to the increase of the global glycolytic activity of lung cancer cells and consequently, the enhancement of their metastatic capability.

Conclusion: We delineated a complex regulatory network that utilized by cancer stem cells to transfer their high metastatic activity to the low-metastatic non-stemness cancer cells through exosomal Mir100hg, thereby providing new mechanistic insights into the communication between two heterogeneous tumor cells. Video Abstract.

Keywords: Exosomal lncRNA; Glycolysis; Mir100hg; miR-15a-5p; miR-31-5p.

Publication types

Video-Audio Media
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma*
Animals
Disease Models, Animal
Glycolysis
Lung
Lung Neoplasms* / genetics
Mice
MicroRNAs* / genetics
Neoplastic Stem Cells
RNA, Long Noncoding* / genetics
Tumor Microenvironment

Substances

RNA, Long Noncoding
MicroRNAs