This study revealed, for the first time, the importance of DANCR in clinical diagnosis and disease progression of HCC.

Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life worldwide, whereas the etiology and pathogenesis of HCC have not been fully determined. In the past few years, many microRNAs (miRNAs) have been proved to have important roles in tumorigenesis of HCC. In this study, we found that miR-23b was significantly upregulated in tumor tissues of HCC patients. Functional tests showed that miR-23b could promote HCC cell proliferation and metastasis in vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a direct target of miR-23b and involved in the promotion effects of miR-23b on HCC tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could interact with the carboxyl terminal region of AKT and suppress AKT/GSK3β/β-catenin pathway in HCC cells. In conclusion, our study revealed important roles of miR-23b and ST7L in progression of HCC.

Background: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.Methods: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.Results: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 (CTCF).Conclusions: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.

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.Methods: A total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27-78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.Results: A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0-28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 μmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III-IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 μmg/L) (P=0.009, OR =3.414). Conclusions:The most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I-II grade,

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