Icaritin inhibits the expression of alpha-fetoprotein in hepatitis B virus-infected hepatoma cell lines through post-transcriptional regulation

Abstract

Although it has showed that icaritin can apparently suppress growth of HCC by reducing the level of AFP, the intrinsic mechanism remains unclear. In this study, we explored the possible mechanism of miRNAs on post-transcriptional regulation of AFP gene, as well as the effects of HBV infection and icaritin in hepatoma cells. The results showed that miR-620, miR-1236 and miR-1270 could bind target sites in the range of 9–18 nt and 131–151 nt downstream of the stop codon in the AFP mRNA 3′-UTR to suppress the expression of AFP. Mutation of these target sites could reverse the effects of these miRNAs. Icaritin (10 μM) might reduce the stability and translational activity of AFP mRNA by increasing the expression levels of these mentioned miRNAs. HBV infection resulted in apparent decreases of these miRNAs and, consequently, increased AFP expression. The results indicated that miR-620, miR-1236 and miR-1270 are critical factors in the post-transcriptional regulation of AFP. Icaritin can counteract the effect of HBV. These findings will contribute to full understanding of the regulatory mechanism of AFP expression in hepatoma cells. And also it revealed a synergistic mechanism of HBV infection and elevation of AFP in the pathogenesis of HCC, as well as the potential clinical significance of icaritin on the therapy of HCC induced by HBV.

MicroRNA‐1270 is associated with poor prognosis and its inhibition yielded anticancer mechanisms in human osteosarcoma

“…It is interesting to notice that, in human lung cancer, miR‐1270 may be possibly associated with multiple downstream target genes, including HDAC4 or GPC5 . In addition, miR‐1270 was suggested to be associated with AFP gene, an oncogenic transcriptional factor, in hepatitis B virus‐infected hepatoma cell lines . Thus, it would be of great interest to both science researchers and clinical physicians to explore the downstream substrates of miR‐1270 in osteosarcoma, therefore to develop new therapeutic targets for treating human patients with osteosarcoma.…”

Icaritin‐induced immunomodulatory efficacy in advanced hepatitis B virus‐related hepatocellular carcinoma: Immunodynamic biomarkers and overall survival

“…Antiinflammatory agents such as flavonoids have an array of immunomodulatory anticancer activities that include immune modulation of the balance between T helper type I (Th1) and type II (Th2) cells 10,21 . Accumulating evidence has revealed multiple anticancer activities of the novel small molecule icaritin through the IL‐6/JAK//STAT3 pathways, 1,22 Th1/Th2‐mediated immunomodulation (Figures 1 and ) and blocking α‐fetoprotein (AFP) in vitro and in vivo 23‐26 . Immunomodulatory anticancer activities induced by icaritin treatment include promotion of CD8 + T cell infiltration and reduced expression of programmed death‐ligand 1 (PD‐L1) in (MDSCs) and neutrophils, 27 and the modulation of immunosuppressive MDSCs 28‐30 and Th1/Th2 associated cytokines (Figure ).…”

A comparative study on the in vitro and in vivo antitumor efficacy of icaritin and hydrous icaritin nanorods

“…ICT exhibits an extensive range of biological and pharmacological activities, such as neuroprotection (Wang et al, 2009), cardiac protection (Zhu & Lou, 2005;Wo et al, 2008;Wang et al, 2009;Zhang et al, 2015), anti-inflammation, immunomodulation (Li et al, 2012;Lai et al, 2013;Liao et al, 2016), and multidrug resistance reversal activity (Liu et al, 2009). Increasing studies proved ICT could suppress growth of different kinds of cancers including breast cancer (Wang & Lou, 2004;Guo et al, 2011;Tiong et al, 2012), prostate cancer (Huang et al, 2007;Sun et al, 2015;Hu et al, 2016;Sun et al, 2016), bladder cancer (Pan et al, 2016), endometrial cancer (Tong et al, 2011), glioblastoma (Han et al, 2015;, colorectal cancer Zhou et al, 2016Zhou et al, 2017), lymphoma (Li et al, 2014;Wu et al, 2015), hepatocellular carcinoma (He et al, 2010;Sun et al, 2013;Zhao et al, 2015;Zhang et al, 2016;Lu et al, 2017), lung cancer (Zheng et al, 2014;Wang et al, 2015), osteosarcoma (Wang & Wang, 2014), chronic/acute myeloid leukemia (Zhu et al, 2011;, esophageal cancer (Han et al, 2018) and hematological malignancies Zhu et al, 2015). Ye and Lou's researches have proved that ICT could induce the proliferation of estrogen receptor (ER)-positive breast cancer MCF-7 cells at submicromolar levels.…”

“…Icaritin (ICT), also named anhydroicaritin in some paper (Zheng et al., 2017 ), is one of the major bioactive flavonoid compounds isolated from traditional Chinese medicine Epimedium Genus (Li et al., 2012 ; Zhao et al., 2015 ; Hu et al., 2016 ; Liao et al., 2016 ; Zhang, 2016 ; Wang et al., 2017 ) and is selected as the chemical index for quality control of Herba Epimedii in Chinese Pharmacopeia (Commission, 2010 ; Li et al., 2015 ). ICT exhibits an extensive range of biological and pharmacological activities, such as neuroprotection (Wang et al., 2009 ), cardiac protection (Zhu & Lou, 2005 ; Wo et al., 2008 ; Wang et al., 2009 ; Zhang et al., 2015 ), anti-inflammation, immunomodulation (Li et al., 2012 ; Lai et al., 2013 ; Liao et al., 2016 ), and multidrug resistance reversal activity (Liu et al., 2009 ).…”