MiR-339-5p Inhibits Ferroptosis by Promoting Autophagic Degradation of FTH1 Through Targeting ATG7 in Liver Cancer Cells.

Background: Liver cancer has a high incidence and mortality rate worldwide, and there is an urgent need to identify new therapeutic strategies and predictive targets to improve the clinical outcomes of advanced liver cancer. Ferroptosis holds promise as a novel strategy for cancer therapy. Epigenetic dysregulation is a hallmark of cancer, and noncoding RNAs are tightly involved in cell fate determination. Therefore, we aimed to identify a novel ferroptosis regulator from aberrantly expressed microRNAs that may serve as a novel biomarker and therapeutic target for liver cancer. Methods: The expression signature and prognostic value of miR-339 was assessed using TCGA data set. The role of miR-339/ATG7/FTH1 axis in liver cancer cells were evaluated through growth curve, colony formation, 7-AAD staining. The role of miR-339 in regulation of ferroptosis was determined by immunofluorescence staining, flow cytometry, and Elisa kits. Results: Here, we showed that miR-339 is aberrantly overexpressed in patients with liver cancer. In addition, miR-339 inhibition dramatically suppresses liver cancer progression. Furthermore, miR-339 silencing drives cell death and inhibits liver cancer progression, indicating that miR-339 may serve as a novel ferroptosis suppressor. Mechanistically, we demonstrated that miR-339 targets ATG7 to facilitate the autophagic degradation of FTH1 and prevent ferroptosis in liver cancer cells. Conclusions: We provide important evidence that the miR-339 inhibition activates of the autophagy pathway to promote ferroptosis by degrading FTH1 in liver cancer cells. We found that miR-339 regulates the balance between ferroptosis and autophagy in liver cancer cells.

Improved clinical outcomes in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus atezolizumab and bevacizumab: a bicentric retrospective study.

PURPOSE: The aim of the present study was to assess the efficacy and safety of transarterial chemoembolization (TACE) combined with atezolizumab and bevacizumab (hereafter, TACE-Atez/Bev) in the treatment of advanced hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: Clinical information was collected from consecutive patients with advanced HCC who received treatment with TACE-Atez/Bev or Atez/Bev from April 2021 and October 2022. Treatment response, overall survival (OS), and progression-free survival (PFS) were the primary outcomes of this study. Adverse events (AEs) were the secondary outcomes. Propensity score matching (PSM) analysis was applied to reduce bias between two groups. RESULTS: This study included 62 patients in the TACE-Atez/Bev group and 77 patients in the Atez/Bev group. The objective response rate (ORR) of the TACE-Atez/Bev group and the Atez/Bev group were 38.7% and 16.9% (P=0.004). However, there was no statistical difference in disease control rate between the two groups (69.4% vs 63.6%, P=0.479). Before PSM, the median OS was 14 months in the TACE-Atez/Bev group and 10 months in the Atez/Bev group (P=0.014). The median PFS in the TACE-Atez/Bev and Atez/Bev groups was 10 months and 6 months, respectively (P=0.001). After PSM, the median OS in the two groups was 14 months and 9 months, respectively (P=0.01). The median PFS was 7 months and 6 months, respectively (P=0.036). Multivariable analysis showed that treatment method was independent prognostic factors affecting OS. CONCLUSIONS: Compared with Atez/Bev treatment, TACE-Atez/Bev showed better OS, PFS, and ORR for Chinese patients with advanced HCC, with an acceptable safety profile.

RNA m6A reader YTHDF1 facilitates inflammation via enhancing NLRP3 translation.

N6-methyladenosine (m6A) modification of mRNAs is involved in multiple essential biological processes, dynamically regulated by m6A "writers", "erasers", and "readers". Yet, the detailed functional roles of RNA m6A reader proteins, such as YTHDFs, are largely unknown. Herein we show that YTHDF1 promotes pro-inflammatory IL-1ß production in macrophages during bacterial infections. YTHDF1 overexpression promotes NLRP3 translation. In vivo knockdown of YTHDF1 facilitates survival in a mouse model of sepsis. Thus, YTHDF1 participates in inflammatory responses and subsequent injuries, serving as a new potential therapeutic target in clinical treatment of inflammatory diseases.

Safety and Feasibility of Microwave Ablation for Hepatocellular Carcinomas in the Elderly: A Systematic Review.

Background: Microwave ablation (MWA) for hepatocellular carcinomas (HCCs) in the elderly has been the subject of new research in recent years. However, there are currently no strong lines of evidence for the prognosis following MWA treatment for HCC in the elderly. Therefore, we conducted a systematic review to assess the safety and feasibility of MWA for HCC in elderly patients. Methods: Up until August 15, 2021, a comprehensive literature search was undertaken in PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases for all published articles. Observational studies reporting the safety and feasibility of MWA for HCC in elderly patients were included. The Newcastle-Ottawa Scale (NOS) was used to measure the quality assessment. Results: Our review, composed of 7 observational studies, including a total of 7,683 HCC patients, looked at the safety and feasibility of MWA for HCC in the elderly. Current lines of evidence on the risks and outcomes of MWA of HCC treatments in elderly patients are discussed. Conclusions: According to our findings, elderly patients, even those with a high comorbidity index, benefited from MWA of HCC similar to younger patients. More clinical data are needed to determine selection criteria for elderly HCC patients to increase the possibility of receiving MWA as a potential lifesaving option. As such, further studies evaluating the outcomes of MWA for HCC treatment modalities in elderly patients are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021273091.

Establishment and Validation of an MTORC1 Signaling-Related Gene Signature to Predict Overall Survival in Patients with Hepatocellular Carcinoma.

BACKGROUND: Accurate and effective biomarkers for the prognosis of patients with hepatocellular carcinoma (HCC) are poorly identified. A network-based gene signature may serve as a valuable biomarker to improve the accuracy of risk discrimination in patients. METHODS: The expression levels of cancer hallmarks were determined by Cox regression analysis. Various bioinformatic methods, such as GSEA, WGCNA, and LASSO, and statistical approaches were applied to generate an MTORC1 signaling-related gene signature (MSRS). Moreover, a decision tree and nomogram were constructed to aid in the quantification of risk levels for each HCC patient. RESULTS: Active MTORC1 signaling was found to be the most vital predictor of overall survival in HCC patients in the training cohort. MSRS was established and proved to hold the capacity to stratify HCC patients with poor outcomes in two validated datasets. Analysis of the patient MSRS levels and patient survival data suggested that the MSRS can be a valuable risk factor in two validated datasets and the integrated cohort. Finally, we constructed a decision tree which allowed to distinguish subclasses of patients at high risk and a nomogram which could accurately predict the survival of individuals. CONCLUSIONS: The present study may contribute to the improvement of current prognostic systems for patients with HCC.

lncRNA PCAT6 facilitates cell proliferation and invasion via regulating the miR-326/hnRNPA2B1 axis in liver cancer.

Liver cancer is one of the most common malignant human tumors with the highest morbidity and mortality rates of all cancer types in China. Evidence suggests that long non-coding RNA prostate cancer-associated transcript 6 (PCAT6) plays an essential role in tumor progression. However, the roles and mechanism of PCAT6 in liver cancer remain unclear. The present study showed that the expression of PCAT6 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) was upregulated in liver cancer tissues compared with non-cancerous tissues and were associated with poor overall survival time, whereas microRNA (miR)-326 expression was downregulated. Moreover, knockdown of PCAT6 significantly inhibited the proliferation and invasion of liver cancer cells in vitro and in vivo. A dual-luciferase reporter gene assay demonstrated that PCAT6 could bind to miR-326 and that hnRNPA2B1 was a direct target gene of miR-326. Mechanistically, silenced PCAT6 suppressed the malignant phenotype of liver cancer cells through upregulating the inhibitory effect of miR-326 on hnRNPA2B1 expression. Taken together, these data demonstrated that knockdown of PCAT6 inhibited liver cancer progression through regulation of the miR-326/hnRNPA2B1 axis, suggesting that PCAT6 functions as an oncogene and may be a useful biomarker for the future diagnosis and treatment of liver cancer.

Electromagnetic navigation to assist with computed tomography-guided thermal ablation of liver tumors.

Purpose: To evaluate the advantages and primary technical efficacy of an electromagnetic (EM) navigation system for computed tomography (CT)-guided thermal ablation of liver tumors.Material and methods: From August 2016 to January 2018, 40 patients scheduled for CT- guided thermal ablation were prospectively enrolled and divided into two groups. Twenty patients underwent CT-guided thermal ablation with an EM navigation system (navigation group), while the other 20 patients underwent conventional CT-guided thermal ablation (control group). Data on skin punctures, instrument adjustments, puncture time to target, CT scans, CT fluoroscopy time and dose-length-product (DLP) were compared between the two groups. Any postoperative complications were recorded and the primary technical efficacy was evaluated four to six weeks after the procedure.Results: All 20 patients in the navigation group successfully underwent EM navigation. Compared to the control group, there were fewer instrument adjustments (mean 2.40 vs. 4.95; p = .003), fewer CT scans (mean 7.10 vs. 10.30; p = .006), less CT fluoroscopy time (mean 40.47 vs. 59.98 s, p = .046), and less DLP (mean 807.39 vs. 1578.67 mGy × cm; p = .001). Although not statistically significant, EM navigation resulted in fewer skin punctures (mean 1.20 vs. 1.25; p = .803) and slightly longer puncture time to target (mean 16.50 vs. 15.20 min; p = .725). No patients experienced major complications and the primary efficacy rate was 90% and 84.21% in the navigation and control groups, respectively (p = .661).Conclusions: EM navigation system optimizes the thermal ablation process and reduces radiation exposure in patients. However, further studies are warranted to determine whether an EM navigation system can improve procedure time, complication rates, and primary technical efficiacy of thermal ablation.