Highlights d Mitochondria-located circRNA SCAR inhibits mROS output and fibroblast activation d circRNA SCAR shuts down mPTP by binding to ATP5B d Lipid-induced ER stress impairs PGC-1a-mediated circRNA SCAR expression d Mitochondria-specific delivery of circRNA SCAR alleviates metaflammation in vivo

No abstract

Background Previous studies have shown the prognostic value of lactate dehydrogenase (LDH) in hepatocellular carcinoma (HCC), but the results are not persuasive. Therefore, the purpose of our study was to quantitatively explore the prognostic value of LDH in hepatocellular carcinoma. Methods We searched the Web of Science, Embase, PubMed, and the Cochrane Library for literature published before October 2018 on the prognostic value of LDH in patients with hepatocellular carcinoma. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to assess the prognostic value of LDH in overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) of HCC. Subgroup analysis, sensitivity analysis, and metaregression were used to explore the source of heterogeneity. Funnel plots with Begg's test and Egger's test were used to detect potential publication biases. Furthermore, combined odds ratios (ORs) were utilized to assess the correlation between LDH and clinicopathological features. Results A total of 10 nonrandomized controlled studies were included in this meta-analysis. The combined effects of LDH on HCC patients' OS, RFS/DFS, and PFS were HR = 2.07, 95% CI: 1.63-2.62, P < 0.001; HR = 1.62, 95% CI: 1.37-1.90, P < 0.001; and HR = 1.96, 95% CI: 1.14-3.36, P = 0.014, respectively. Subgroup analysis and sensitivity analysis showed that the outcome was stable, and the results of the metaregression also identified statistical models as an important source of heterogeneity. Potential publication bias was detected in the OS studies, so the trim-and-fill method was used to explore publication bias, and the results showed stability. Furthermore, the combined OR suggests that LDH was significantly correlated with gender, Child-Pugh grade, alpha-fetoprotein, vascular invasion, and tumor size. Conclusions Preoperative LDH elevation is significantly associated with poor prognosis in patients with HCC, which may be a promising factor in assessing the prognosis of patients with HCC.

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI‐HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial‐mesenchymal transition (EMT)‐like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR‐625‐5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR‐625‐5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.

No abstract

No abstract