Open AccessHypoxic colorectal cancer-secreted exosomes deliver miR-210-3p to normoxic tumor cells to elicit a protumoral effect
Author(s) -
Liuqing Ge,
Feng Zhou,
Jiayan Nie,
Xiaobing Wang,
Qiu Zhao
Publication year - 2021
Publication title -
experimental biology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 146
eISSN - 1535-3702
pISSN - 1535-3699
DOI - 10.1177/15353702211011576
Subject(s) - microvesicles , colorectal cancer , cancer research , tumor microenvironment , carcinogenesis , tumor progression , medicine , cancer , mouse model of colorectal and intestinal cancer , cancer cell , hypoxia (environmental) , microrna , immunology , biology , chemistry , tumor cells , biochemistry , organic chemistry , oxygen , gene
Hypoxia, the most common feature in the tumor microenvironment, is closely related to tumor malignant progression and poor patient's prognosis. Exosomes, initially recognized as cellular "garbage dumpsters", are now known to be important mediums for mediating cellular communication in tumor microenvironment. However, the mechanisms of hypoxic tumor cell-derived exosomes facilitate colorectal cancer progression still need further exploration. In the present study, we found that exosomes from hypoxic colorectal cancer cells (H-Exos) promoted G1-S cycle transition and proliferation while preventing the apoptosis of colorectal cancer cells by transmitting miR-210-3p to normoxic tumor cells. Mechanistic investigation indicated that miR-210-3p from H-Exos elicited its protumoral effect via suppressing CELF2 expression. A preclinical study further confirmed that H-Exos could promote tumorigenesis in vivo . Clinically, the expression of miR-210-3p in circulating plasma exosomes was markedly upregulated in colorectal cancer patients, which were closely associated with multiple unfavorable clinicopathological features. Taken together, these results suggest that hypoxia may stimulate colorectal cancer cells to secrete miR-210-3p-enriched exosomes in tumor microenvironment, which elicit protumoral effects by inhibiting CELF2 expression. These findings provide new insights on the mechanism of colorectal cancer progression and potential therapeutic targets for colorectal cancer.