MiRNA-22 inhibits oncogene galectin-1 in hepatocellular carcinoma

Abstract

Hepatic stellate cells (HSCs) induce immune privilege and promote hepatocellular carcinoma (HCC) by suppressing the immune system. On the other hand, galectin-1 and miRNA-22 (miR-22) are dysregulated in HCC and serve as prognostic indicators for patients. In this study, therefore, we measured galectin-1 and miR-22 expression in HSCs isolated from HCC tissues (Ca-HSCs), and in normal liver tissues (N-HSCs) as a control. We also investigated the apoptosis rate among T cells and the production of cytokines (IFN-η and IL-10) in HSCs co-cultured with T cells. And we used immunohistochemical staining to tested for correlation between galectin-1 expression, CD3 expression and clinicopathological features in 162 HCC patients. Our results showed that galectin-1 expression was much higher in Ca-HSCs than in N-HSCs. Overexpression of galectin-1 promoted HSC-induced T cell apoptosis and cytokine production (IFN-η and IL-10), while miR-22 expression inhibited it. Galectin-1 expression correlated negatively with miR-22 expression in HSCs. High galectin-1 and low CD3 expression levels were associated with poor prognosis in HCC patients. These results suggest that the immunosuppressive microenvironment promoted by HSC-derived galectin-1 in HCC can be inhibited by miR-22. Galectin-1 and miR-22 could potentially serve as prognostic markers and therapeutic targets in HCC.

Contribution of galectin-1, a glycan-binding protein, to gastrointestinal tumor progression

“…While in human normal or adjacent non-tumor liver tissues Gal-1 is expressed at low levels, in HCC its expression is dramatically up-regulated[ 62 - 66 ]. The transcription start site of Gal-1 gene promoter was frequently methylated in non-tumor liver, whereas it was hypomethylated in HCC tissues[ 63 ].…”

“…Besides, Gal-1 was significantly increased in HCC samples from patients with metastasis compared to those harboring a non-metastatic primary tumor and it was found accumulated in the stroma surrounding tumor hepatocytes[ 64 ]. Accordingly, Gal-1 was highly expressed in stromal α-SMA-positive cells in HCC, indicating that Gal-1 is overexpressed in hepatic stellate cells (HSCs)[ 66 ].…”

“…Elevated Gal-1 expression in HCC was significantly associated with tumor aggressiveness (vascular invasion, incomplete encapsulation, poor differentiation and large tumor size), dissemination and enhanced risk of post-operative recurrence[ 65 ]. Additionally, high stromal Gal-1 expression in HCC was correlated with tumor size, TNM stage and distant metastasis and negatively correlated with patient prognosis[ 66 ]. Moreover, in HCC samples, an inverse correlation between miR-22 and Gal-1 expression was found[ 66 ].…”

“…Additionally, high stromal Gal-1 expression in HCC was correlated with tumor size, TNM stage and distant metastasis and negatively correlated with patient prognosis[ 66 ]. Moreover, in HCC samples, an inverse correlation between miR-22 and Gal-1 expression was found[ 66 ]. miR-22 is downregulated in HCC[ 67 ] and Gal-1 has been predicted to be a target of miR-22.…”

Investigating the potential of circulating microRNAs as non-invasive biomarkers in cirrhosis and hepatocellular carcinoma

“…Several functional targets for miRNA-22-3p have been described, such as HDAC4 (which is needed for cell proliferation 429 ), CD147 431 (a potential HCC prognostic marker 432 ), galectin 9 433,434 and galectin 1. 435 Interestingly, both galectins have been previously linked with angiogenesis 436 as well as HCC development. 437 In addition to a possible tumour suppressor role, increased liver tissue miRNA-22-3p has also been described in the study of other diseases.…”