Journal
CANCER LETTERS
Volume 497, Issue -, Pages 137-153Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.10.023
Keywords
Extracellular vesicles; MicroRNAs; Macrophage polarization; Hepatocellular carcinomas; Arsenic poisoning
Categories
Funding
- Natural Science Foundations of China [81730089, 81872665]
- National Key Research and Development Program of China [2016YFE0204900]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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Arsenic, a known human carcinogen, promotes the progression of liver cancer cells by modulating miRNA levels and inducing tumor invasion. This study reveals the mechanism by which arsenic exposure leads to increased miR-15b levels and promotes the proliferation and metastasis of hepatocellular carcinoma cells by downregulating the tumor suppressor LATS1.
Arsenic, a human carcinogen, causes various human cancers, including those of the skin, lung, and liver. Hepatocellular carcinomas (HCCs), which have high mortality, are common malignancies worldwide. Tumor associated macrophages (TAMs), which are considered to be similar to M2-polarized macrophages, promote tumor invasion and progression. Small non-coding RNAs (miRNAs) regulate expression of genes involved in progression of various malignancies. Extracellular vesicles (EVs), as mediators of cell communication, pass specific miRNAs directly from TAMs to tumor cells, promoting tumor pathogenesis and metastasis. In HCCs, large tumor suppressor kinase 1 (LATS1), functions as a tumor suppressor. However, the molecular mechanism by which miRNA modulates LATS1 expression in HCCs remains unclear. The results show that exposure to arsenite, increased miR-15b levels and induced M2 polarization of THP-1 cells. Elevated levels of miR-15b were transferred from arsenite-treated-THP-1 (As-THP-1) cells to HCC cells via miR-15b in EVs inhibited activation of the Hippo pathway by targeting LATS1, and was involved in promoting the proliferation, migration, and invasion of HCC cells. In conclusion, miR-15b in EVs from As-THP-1 cells is transferred to HCC cells, in which it targets and downregulates LATS1 expression and promotes the proliferation, migration, and invasion of HCC cells.
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