Long noncoding ribonucleic acid (lncRNA) X-inactive-specific transcript (Xist) was
reported to affect cell proliferation and metastasis in hepatocellular carcinoma (HCC).
However, there are rare reports focusing on the diagnostic evaluation and regulatory
mechanism of Xist expression from peripheral blood cells of patients with HCC.
In this study, a cohort of 206 female participants including healthy volunteers (HVs)
and patients with chronic hepatitis B (CHB), cirrhosis and HCC was recruited. Coculture
system was used to evaluate the effects of exosomal JPX transcript, XIST activator (Jpx)
on Xist expression of blood cells.
First, Xist expressions of both peripheral blood mononuclear cells and granulocytes
were upregulated in female patients with HCC, and showed significantly increased
discriminatory power when differentiating female patients with early-stage HCC from
controls or differentiating female patients with HCC from patients with CHB and
cirrhosis, compared with alpha fetoprotein (AFP). Then, another lncRNA Jpx that was an
activator of Xist was upregulated in exosomes, mononuclear cells and granulocytes of
female patients with HCC. Furthermore, our results showed that Jpx could be delivered
from HCC cells to blood cells via exosomes and activate Xist expression
of blood cells by repressing the transregulatory effects of CCCTC-binding factor
This study revealed an exosome-mediated regulation of Xist expression in blood cells
and suggested that Xist expressions of mononuclear cells and granulocytes would be
promising biomarkers for diagnosis of female patients with HCC.