期刊
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
卷 17, 期 7, 页码 953-964出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijms.44377
关键词
miR-19a; miR-19b-1; lung cancer; nasopharyngeal carcinoma; MHC class I gene; interferon-inducible gene; interleukin-related gene
资金
- National Natural Science Foundation of China [81872209, 81672689, 81372896, 81172587, 81600086, 81770100, 81600488, 81870602, 81702778, 81560441, 81760491, 81660485]
- Natural Science Foundation of Guangdong Province of China [2014A030313294]
- Science and Technology Planning Project of Guangdong Province of China [2009B060300008, 2013B060300013, 2017A010105017, 2017A030303018, 2015A030302024]
- China Postdoctoral Science Foundation [2015M572338, 2016T90792, 2017M622740, 2018T110884]
- Medical Scientific Research Foundation of Guangdong Province of China [A2017420]
MicroRNA-19 (miR-19) is identified as the key oncogenic component of the miR-17-92 cluster. When we explored the functions of the dysregulated miR-19 in lung cancer, microarray-based data unexpectedly demonstrated that some immune and inflammatory response genes (i.e., IL32, IFI6 and IFIT1) were generally down-regulated by miR-19 overexpression in A549 cells, which prompted us to fully investigate whether the miR-19 family (i.e., miR-19a and miR-19b-1) was implicated in regulating the expression of immune and inflammatory response genes in cancer cells. In the present study, we observed that miR-19a or miR-19b-1 overexpression by miRNA mimics in the A549, HCC827 and CNE2 cells significantly downregulated the expression of interferon (IFN)-regulated genes (i.e., IRF7, IFI6, IFIT1, IFITM1, IFI27 and IFI44L). Furthermore, the ectopic miR-19a or miR-19b-1 expression in the A549, HCC827, CNE2 and HONE1 cells led to a general downward trend in the expression profile of major histocompatibility complex (MHC) class I genes (such as HLA-B, HLA-E, HLA-F or HLA-G); conversely, miR-19a or miR-19b-1 inhibition by the miRNA inhibitor upregulated the aforementioned MHC Class I gene expression, suggesting that miR-19a or miR-19b-1 negatively modulates MHC Class I gene expression. The miR-19a or miR-19b-1 mimics reduced the expression of interleukin (IL)-related genes (i.e., IL1B, IL11RA and IL6) in the A549, HCC827, CNE2 or HONE1 cells. The ectopic expression of miR-19a or miR-19b-1 downregulated IL32 expression in the A549 and HCC827 cells and upregulated IL32 expression in CNE2 and HONE1 cells. In addition, enforced miR-19a or miR-19b-1 expression suppressed IL-6 production by lung cancer and nasopharyngeal carcinoma (NPC) cells. Taken together, these findings demonstrate, for the first time, that miR-19 can modulate the expression of IFN-induced genes and MHC class I genes in human cancer cells, suggesting a novel role of miR-19 in linking inflammation and cancer, which remains to be fully characterized.
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