Open AccessHIF‐1α downregulation of miR‐433‐3p in adipocyte‐derived exosomes contributes to NPC progression via targeting SCD1
Author(s) -
Yin Haimeng,
Qiu Xiaoxia,
Shan Ying,
You Bo,
Xie Lixiao,
Zhang Panpan,
Zhao Jianmei,
You Yiwen
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14829
Subject(s) - cancer research , downregulation and upregulation , microrna , microvesicles , carcinogenesis , biology , tumor progression , transcription factor , nasopharyngeal carcinoma , tumor microenvironment , adipocyte , cell growth , microbiology and biotechnology , cancer , medicine , endocrinology , gene , tumor cells , adipose tissue , genetics , radiation therapy
Resident adipocytes under a hypoxic tumor microenvironment exert an increasingly important role in cell growth, proliferation, and invasion in cancers. However, the communication between adipocytes and cancer cells during nasopharyngeal carcinoma (NPC) progression is poorly understood. Here, we demonstrate that hypoxic adipocyte‐derived exosomes are key information carriers that transfer low expression of miR‐433‐3p into NPC cells. In addition, luciferase reporter assays detected that hypoxia inducible factor‐1α (HIF‐1α) induced miR‐433‐3p transcription through five binding sites at its promoter region. Concordantly, the low expression of miR‐433‐3p promoted proliferation, migration, and lipid accumulation in NPC cells via targeting stearoyl‐CoA desaturase 1 (SCD1) are suggested by functional studies. Consistent with these findings, in tumor‐bearing mice, NPC cells with low HIF‐1α expression, high miR‐433‐3p expression, and low SCD1 expression were equally endowed with remarkably reduced potential of tumorigenesis. Collectively, our study highlights the critical role of the HIF‐1α‐miR‐433‐3p‐SCD1 axis in NPC progression, which can serve as a mechanism‐based potential therapeutic approach.