Journal
BMC GASTROENTEROLOGY
Volume 19, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12876-019-1048-3
Keywords
MiRNA; miR-122; Toll like receptor; Hepatocytes
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81202296]
- Heilongjiang Postdoctoral Grant [LBH-Q15083]
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Background: Hepatocellular carcinoma (HCC) is a kind of malignancies to impact human health. It has been reported that aberrant toll-like receptor (TLR) signaling may contribute to the development and progression of HCC, especially TLR4. MiR-122, which extensively involved in hepatitis virus infection and the apoptosis of hepatoma cells, might be decreased in HCC patients livers. The hypothesis of this study was whether miR-122 plays a role in inflammatory pathways through regulating TLR4 expression in hepatoma cells. Methods: The expression of miR-122 in the tissues of HCC patients compared to controls in TCGA datasets was analyzed. The relationship between miR-122 and TLR4 was detected in HCC cell lines by increasing/decreasing miR-122 expression. The target of miR-122 on TLR4 was confirmed by luciferase reporter assays. The proliferation of HCC cells and production of proinflammatory cytokines were measured with miR-122 upregulation and inhibition. Results: We found that the expression of miR-122 was decreased in HCC tissues and showed the diagnostic capacity for HCC in TCGA datasets. MiR-122 and TLR4 expression have negative correlation in normal liver cells and HCC cells. Upregulation of miR-122 significantly inhibited TLR4 expression in hepatoma cells, including in hepatoma cells with the induction of LPS, while knocking down miR-122 increased TLR4 expression. By screening potential miR-122 targets among TLR4, we found that there was a putative miR-122 target in TLR4 3 ' UTR. Mutations in the nt1603-nt1609 region of TLR4 3 ' UTR abandoned the impact of miR-122 on TLR4 expression. Over-expression/down-expression of miR-122 could influence the proliferation and the expression of natural immune factors. Conclusions: MiR-122 might target TLR4 and regulate host innate immunity in hepatoma cells, which revealed a new molecular mechanism of miR-122 on the regulation of innate immunity.
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